Musculoskeletal disorders represent a major cause of disability and morbidity globally and result in enormous costs for health and social care systems. Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders. Novel biological therapies that can effectively treat joint and spine degeneration are high priorities in regenerative medicine. Mesenchymal stem cells (MSCs) isolated from bone marrow (BM-MSCs), adipose tissue (AD-MSCs) and umbilical cord (UC-MSCs) show considerable promise for use in cartilage and intervertebral disc (IVD) repair. This review article focuses on stem cell-based therapeutics for cartilage and IVD repair in the context of the rising global burden of musculoskeletal disorders. We discuss the biology MSCs and chondroprogenitor cells and specifically focus on umbilical cord/Wharton’s jelly derived MSCs and examine their potential for regenerative applications. We also summarize key components of the molecular machinery and signaling pathways responsible for the control of chondrogenesis and explore biomimetic scaffolds and biomaterials for articular cartilage and IVD regeneration. This review explores the exciting opportunities afforded by MSCs and discusses the challenges associated with cartilage and IVD repair and regeneration. There are still many technical challenges associated with isolating, expanding, differentiating, and pre-conditioning MSCs for subsequent implantation into degenerate joints and the spine. However, the prospect of combining biomaterials and cell-based therapies that incorporate chondrocytes, chondroprogenitors and MSCs leads to the optimistic view that interdisciplinary approaches will lead to significant breakthroughs in regenerating musculoskeletal tissues, such as the joint and the spine in the near future.
View PaperLow-back pain is the most common health problem for men and women between 20 and 50 years of age, resulting in 13 million doctor visits in the US annually, with significant costs to society in terms of lost time from work and direct and indirect medical expenses. Although the exact origin of most cases of low-back pain remains unknown, it is understood that degenerative damage to the intervertebral disc (IVD) plays a central role in the pathogenic mechanism leading to this disorder. Current treatment modalities for disc-related back pain (selective nerve root blocks, surgical discectomy and fusion) are costly procedures aimed only at alleviating symptoms. Consequently, there is growing interest in the development of novel technologies to repair or regenerate the degenerated IVD. Recently, mesenchymal stem cells (MSCs) have been found to possess the capacity to differentiate into nucleus pulposus–like cells capable of synthesizing a physiological, proteoglycan-rich extracellular matrix characteristic of healthy IVDs. In this article, the authors review the use of MSCs for repopulation of the degenerating IVD. Although important obstacles to the survival and proliferation of stem cells within the degenerating disc need to be overcome, the potential for MSC therapy to slow or reverse the degenerative process remains substantial.
View PaperLow back pain with resultant loss of function, decreased productivity, and high economic costs is burdensome for both the individual and the society. Evidence suggests that intervertebral disc pathology is a major contributor to spine-related pain and degeneration. When commonly used conservative therapies fail, traditional percutaneous or surgical options may be beneficial for pain relief but are suboptimal because of their inability to alter disc microenvironment catabolism, restore disc tissue, and/or preserve native spine biomechanics. Percutaneously injected Multipotent Mesenchymal Stem Cell (MSC) therapy has recently gained clinical interest for its potential to revolutionarily treat disc-generated (discogenic) pain and associated disc degeneration. Unlike previous therapies to date, MSCs may uniquely offer the ability to improve discogenic pain and provide more sustained improvement by reducing disc microenvironment catabolism and regenerating disc tissue. Consistent treatment success has the potential to create a paradigm shift with regards to the treatment of discogenic pain and disc degeneration.
View PaperPatients often present to spine clinic with evidence of intervertebral disc degeneration (IDD). If conservative management fails, a safe and effective injection directly into the disc might be preferable to the risks and morbidity of surgery.
View PaperThe current study evaluated 5 patients with ankylosing spondylitis (AS). Patients received intravenous transfusions of umbilical cord mesenchymal stem cells (uMSCs). All therapeutic and adverse responses were assessed and recorded during uMSC therapy. No severe adverse reactions were observed in any of the patients, although a slight transient fever was observed in 3 patients within 2‑6 h of intravenous administration of uMSCs. Following treatment, the Bath Ankylosing Spondylitis Disease Activity and Bath Ankylosing Spondylitis Metrology Indices decreased, however the Bath Ankylosing Spondylitis Functional Index increased. The erythrocyte sedimentation rate in 3 patients was reduced and C‑reactive protein levels in 1 patient were markedly reduced. The symptoms of AS were alleviated in all patients. The present study indicates that intravenous transfusion of uMSCs is safe and well tolerated by patients and that it effectively alleviates disease activity and clinical symptoms. In the future, a larger cohort of patients with AS should be recruited to enable the systemic evaluation of uMSC therapy.
View PaperIn order to investigate the interaction between human Wharton’s jelly cells (WJCs) and degenerative nucleus pulposus cells (NPCs), human WJCs were cocultured with degenerative NPCs with or without direct cell-cell contact. WJCs were isolated from the human umbilical cord and degenerative NPCs were isolated from the surgically obtained degenerative intervertebral disc tissue. The isolated WJCs positively expressed CD73, CD105, CD90, CD29, CD166 and human leukocyte antigen (HLA)-ABC, but negatively expressed CD34, CD45, and HLA-DR. After coculturing with 3 different WJCs:NPCs ratios for 7 days, the real-time polymerase chain reaction showed that the relative gene expression of NP-marker genes [aggrecan, type II collagen, and SRY-type HMG box-9 (SOX-9)] was significantly upgraded in all coculture groups (all P values < 0.05 compared with control groups). Coculture either with or without cell-cell contact significantly activated the expression of NP-maker genes than controls, but coculture with cell-cell contact yielded a higher gene expression than coculture without cell-cell contact. In coculturing with cell-cell contact and WJCs:NPCs of 25:75, the relative gene expression of aggrecan, type II collagen, SOX-9 for WJCs yielded the highest increase by 721-, 1507-, and 1463-folds, respectively (all P < 0.05 compared with WJCs control). In contrast, the highest relative gene expression of aggrecan, type II collagen, SOX-9 for NPCs was 112-, 84-, 109-folds, respectively, in coculture with cell-cell contact and in WJCs: NPCs of 75:25 (all P < 0.05 compared with NPCs control). In conclusion, the data indicated that coculturing human WJCs with degenerative NPCs induced the NP-like cell differentiation of WJCs and restored the biological status of degenerative NPCs and coculture WJCs and NPCs with direct cell-cell contact yielded more favorable gene expressions
View PaperIntervertebral disc (IVD) degeneration is characterized by the loss of nucleus pulposus (NP), which is a common cause for lower back pain. Although, currently, there is no cure for the degenerative disc disease, stem cell therapy is increasingly being considered for its treatment. In this study, we investigated the feasibility and efficacy of human umbilical cord mesenchymal stem cells (MSCs) and chondroprogenitor cells (CPCs) derived from those cells to regenerate damaged IVD in a rabbit model. Transplanted cells survived, engrafted and dispersed into NP in situ. Significant improvement in the histology, cellularity, extracellular matrix proteins, and water and glycosaminoglycan contents in IVD recipients of CPCs was observed compared to MSCs. In addition, IVDs receiving CPCs exhibited higher expression of NP-specific human markers, SOX9, aggrecan, collagen 2, FOXF1 and KRT19. The novelty of the study is that in vitro differentiated CPCs derived from umbilical cord MSCs, demonstrated far greater capacity to regenerate damaged IVDs, which provides basis and impetus for stem cell based clinical studies to treat degenerative disc disease.
View PaperChronic low back pain is one of the major causes of disability and thus has a major socioeconomic impact. Intervertebral disc degeneration is the main cause of chronic low back pain. Treatment for chronic discogenic low back pain has traditionally been limited to either conservative management or surgical fusion. If conservative treatment fails, then surgical fusion is commonly considered. Current treatments are limited to treat the symptoms and not the underlying biologic alterations of the disc.
View PaperSeveral cell-based therapies have been proposed in recent years the management of low back pain, including the injection of medicinal signaling cells or mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). However, there is only emerging clinical evidence to support their use at this time.
View PaperLow back pain is the main cause of disability and is associated with intervertebral disc degeneration. Contemporary treatments are limited to palliative therapeutics or aggressive surgical interventions; however, current advancements in cell therapy offer to fill this breach. Clinical data suggest that cell transplantation can accomplish pain relief without any observed adverse effects. Despite a large variety of preclinical studies and preliminary clinical investigations, controversy remains on the optimal cell type and transplantation strategies. The translational potential of this article lies in the aim to update
View PaperIt is the promise of regeneration and therapeutic applications that has sparked an interest in mesenchymal stem cells (MSCs). Following infusion, MSCs migrate to sites of injury or inflammation by virtue of their homing property. To exert optimal clinical benefits, systemically delivered MSCs need to migrate efficiently and in adequate numbers to pathological areas in vivo. However, underlying molecular mechanisms responsible for MSC migration are still not well understood. The Wharton’s jelly (WJ) of the umbilical cord is an attractive source of MSCs for stem cell therapy because of its abundant availability and painless collection. In this study, we attempted to identify the role of nonmuscle myosin II (NMII), if any, in the migration of WJ-derived MSCs (WJ-MSCs). Expression of NMII isoforms, NMIIA, and NMIIB was observed both at RNA and protein levels in WJ-MSCs. Inhibition of NMII or its regulator ROCK, by pharmacological inhibitors, resulted in significant reduction in the migration of WJ-MSCs as confirmed by the scratch migration assay and time-lapse microscopy. Next, trying to dissect the role of each NMII isoform in migration of WJ-MSCs, we found that siRNA-mediated downregulation of NMIIA, but not NMIIB expression, led to cells failing to retract their trailing edge and losing cell–cell cohesiveness, while exhibiting a nondirectional migratory pathway. Migration, moreover, is also dependent on optimal affinity adhesion, which would allow rapid attachment and release of cells and, hence, can be influenced by extracellular matrix (ECM) and adhesion molecules. We demonstrated that inhibition of NMII and more specifically NMIIA resulted in increased gene expression of ECM and adhesion molecules, which possibly led to stronger adhesions and, hence, decreased migration. Therefore, these data suggest that NMII acts as a regulator of cell migration and adhesion in WJ-MSCs.
View PaperPsoriasis is an incurable immune-mediated disease, which affects approximately 2% of the world’s population. Current treatments, including newly emerged biologic agents, have some limitations.1 Here, we report 2 cases of psoriasis vulgaris treated by umbilical cord-derived mesenchymal stem cells (UC-MSCs). In these 2 cases, both of the patients remained relapse free for 4 or 5 years.
View PaperMesenchymal stem cells (MSCs) are multipotent cells that have the capability of differentiating into adipogenic, osteogenic, chondrogenic, and neural cells. With these multiple capabilities, MSCs have been highly regarded as effective transplantable cell source for regenerative medicine. A large bank of these cells can be found in several regions of the human umbilical cord (hUC) including the umbilical cord lining, the subendothelial layer, the perivascular zone, and most importantly in Wharton’s jelly (WJ). These cells, all umbilical cord-derived MSCs, are very durable, have large loading capacities, and are considered ethical to harvest because the umbilical cord is often considered a waste. These logistical advantages make WJ as appealing source of stem cells for transplant therapy. In particular, WJ is a predominantly good source of cells because MSCs in WJ (WJ-MSC) are maintained in a very early embryological phase and therefore have retained some of the primitive stemness properties. WJ-MSCs can easily differentiate into a plethora of cell types leading to a variety of applications. In addition, WJ-MSCs are slightly easier to harvest compared to other MSCs (such as bone marrow-derived MSCs). The fascinating stemness properties and therapeutic potential of WJ-MSCs provide great promise in many aspects of regenerative medicine and should be considered for further investigations as safe and effective donor cells for transplantation therapy in many debilitating disorders, which are discussed here. We previously reviewed WJ-MSCs therapeutic potential [1] and now provide an update on their recent preclinical and clinical applications.
View PaperThe human umbilical cord is a rich source of autologous stem and progenitor cells. Interestingly, subpopulations of these, particularly mesenchymal-like cells from both cord blood and the cord stroma, exhibited a potential to be differentiated into neuron-like cells in culture. Umbilical cord blood stem cells have demonstrated efficacy in reducing lesion sizes and enhancing behavioral recovery in animal models of ischemic and traumatic central nervous system (CNS) injury. Recent findings also suggest that neurons derived from cord stroma mesenchymal cells could alleviate movement disorders in hemiparkinsonian animal models. We review here the neurogenic potential of umbilical cord stem cells and discuss possibilities of their exploitation as an alternative to human embryonic stem cells or neural stem cells for transplantation therapy of traumatic CNS injury and neurodegenerative diseases.
View PaperUmbilical cord matrix or Wharton’s jelly-derived stromal cells (WJ-MSCs) are an easily accessible source of mesenchymal-like stem cells. Recent studies describe a hypoimmunogenic phenotype, multipotent differentiation potential, and trophic support function for WJ-MSCs, with variable clinical benefit in degenerative disease models such as stroke, myocardial infarction, and Parkinson’s disease. It remains unclear whether WJ-MSCs have therapeutic value for multiple sclerosis (MS), where autoimmune-mediated demyelination and neurodegeneration need to be halted. In this study, we investigated whether WJ-MSCs possess the required properties to effectively and durably reverse these pathological hallmarks and whether they survive in an inflammatory environment after transplantation. WJ-MSCs displayed a lowly immunogenic phenotype and showed intrinsic expression of neurotrophic factors and a variety of anti-inflammatory molecules. Furthermore, they dose-dependently suppressed proliferation of activated T cells using contact-dependent and paracrine mechanisms. Indoleamine 2,3-dioxygenase 1 was identified as one of the main effector molecules responsible for the observed T-cell suppression. The immune-modulatory phenotype of WJ-MSCs was further enhanced after proinflammatory cytokine treatment in vitro (licensing). In addition to their effect on adaptive immunity, WJ-MSCs interfered with dendritic cell differentiation and maturation, thus directly affecting antigen presentation and therefore T-cell priming. Systemically infused WJ-MSCs potently but transiently ameliorated experimental autoimmune encephalomyelitis (EAE), an animal model for MS, when injected at onset or during chronic disease. This protective effect was paralleled with a reduction in autoantigen-induced T-cell proliferation, confirming their immunomodulatory activity in vivo. Surprisingly, in vitro licensed WJ-MSCs did not ameliorate EAE, indicative of a fast rejection as a result of enhanced immunogenicity. Collectively, we show that WJ-MSCs have trophic support properties and effectively modulate immune cell functioning both in vitro and in the EAE model, suggesting WJ-MSC may hold promise for MS therapy. Future research is needed to optimize survival of stem cells and enhance clinical durability.
View PaperWharton’s jelly (WJ) is a gelatinous tissue within the umbilical cord that contains myofibroblast-like stromal cells. A unique cell population of WJ that has been suggested as displaying the stemness phenotype is the mesenchymal stromal cells (MSCs). Because MSCs’ stemness and immune properties appear to be more robustly expressed and functional which are more comparable with fetal than adult-derived MSCs, MSCs harvested from the “young” WJ are considered much more proliferative, immunosuppressive, and even therapeutically active stem cells than those isolated from older, adult tissue sources such as the bone marrow or adipose. The present review discusses the phenotypic characteristics, therapeutic applications, and optimization of experimental protocols for WJ-derived stem cells. MSCs derived from WJ display promising transplantable features, including ease of sourcing, in vitro expandability, differentiation abilities, immune-evasion and immune-regulation capacities. Accumulating evidence demonstrates that WJ-derived stem cells possess many potential advantages as transplantable cells for treatment of various diseases (e.g., cancer, chronic liver disease, cardiovascular diseases, nerve, cartilage and tendon injury). Additional studies are warranted to translate the use of WJ-derived stem cells for clinical applications.
View PaperThis review focuses on the therapeutic potential of stem cells harvested from the Wharton’s Jelly of the human umbilical cord. Recently, investigators have found that a potent stem cell population exists within the Wharton’s Jelly. In this review, the authors define a new subset of stem cells, termed perinatal stem cells, and compare them to other sources of stem cells. Furthermore, cryopreservation of Wharton’s Jelly stem cells is described for potential use in future cell based therapies and/or regenerative medicine applications. Current evidence of the application of mesenchymal stem cells from various sources in both pre-clinical and clinical trials is reviewed in the context of potential indications of use for Wharton’s Jelly derived mesenchymal stem cells.
View PaperMesenchymal stromal/stem cells (MSCs) exist in almost all tissues, possessing the potential to dierentiate into specialized cell types and exert immunomodulatory functions. Thus, they have attracted much attention as a promising therapeutic candidate. Recent studies have demonstrated that paracrine signaling is mainly responsible for the involvement of MSCs in the modulation of immune responses and the progression of diseases. Through release of secretome consisting of a diverse range of cytokines, chemokines, and extracellular vesicles (EVs), MSCs convey regulatory messages to recipient immune cells in the microenvironment. In this review, we focus on the recent advances in how MSCs contribute to immunomodulation through the secretion of paracrine factors. The further improved understanding of the molecular mechanism underlying the interactions between MSCs and immune cells highlights the paracrine biology of MSCs in the modulation of the immune microenvironment and promotes the clinical application of MSCs in regenerative medicine and immune diseases.
View PaperAging tissues experience a progressive decline in homeostatic and regenerative capacities, which has been attributed to degenerative changes in tissue-specific stem cells, stem cell niches and systemic cues that regulate stem cell activity. Understanding the molecular pathways involved in this age-dependent deterioration of stem cell function will be critical for developing new therapies for diseases of aging that target the specific causes of age-related functional decline. Here we explore key molecular pathways that are commonly perturbed as tissues and stem cells age and degenerate. We further consider experimental evidence both supporting and refuting the notion that modulation of these pathways per se can reverse aging phenotypes. Finally, we ask whether stem cell aging establishes an epigenetic ‘memory’ that is indelibly written or one that can be reset.
View PaperIn recent years, human mesenchymal stem cells (MSC) have been extensively studied. Their key characteristics of long-term self-renewal and a capacity to differentiate into diverse mature tissues favor their use in regenerative medicine applications. Stem cells can be found in embryonic and extraembryonic tissues as well as in adult organs. Several reports indicate that cells of Wharton’s jelly (WJ), the main component of umbilical cord extracellular matrix, are multipotent stem cells, expressing markers of bone marrow mesenchymal stem cells (BM-MSC), and giving rise to different cellular types of both connective and nervous tissues. Wharton’s jelly mesenchymal stem cells (WJ-MSC) express markers previously characterized in embryonic stem cells (ESC), such as Nanog and Oct3/4A. WJ-MSC further emerge as promising hypoimmunogenic cells, due to the expression of molecules able to modulate NK cells and expand regulatory T-cell populations. Moreover, it is now accepted that the differentiative capacities of such cells span all the mesoderm-derived tissues, extending to neuroectodermal as well as endodermal lineages. In this review, we compare very recent data on the potential of WJ-MSC to undergo hepatocyte- like differentiation with the results obtained from other adult MSC populations. Data in the literature strongly suggest that WJ-MSC can differentiate into diverse cell types, showing a unique ability to cross lineage borders. This, together with their in vitro proliferative potential and their immunoregulatory features, renders these cells extremely promising for regenerative medicine applications in different pathological settings.
View PaperCutaneous wounds persist as a health care crisis in spite of increased understanding of the cellular and molecular responses to injury. Contributing significantly to this crisis is the lack of reliable therapies for treatment of wounds that are slow to heal including chronic wounds and deep dermal wounds that develop hypertrophic scars. This article will review the growing evidence demonstrating the promise of multipotent mesenchymal stem/stromal (MSCs) for the treatment of impaired wound healing. MSCs are often referred to as mesenchymal stem cells despite concerns that these cells are not truly stem cells given the lack of evidence demonstrating self-renewal in vivo. Regardless, abundant evidence demonstrates the therapeutic potential of MSCs for repair and regeneration of damaged tissue due to injury or disease. To date, MSC treatment of acute and chronic wounds results in accelerated wound closure with increased epithelialization, granulation tissue formation and angiogenesis. Although there is evidence for MSC differentiation in the wound, most of the therapeutic effects are likely due to MSCs releasing soluble factors that regulate local cellular responses to cutaneous injury. Important challenges need to be overcome before MSCs can be used effectively to treat wounds that are slow to heal.
View PaperStem cell therapy can be used for alleviating the neuropathic pain induced by spinal cord injuries (SCIs). However, survival and differentiation of stem cells following their transplantation vary depending on the host and intrinsic factors of the cell. Therefore, the present study aimed to determine the effect of stem cells derived from bone marrow (BM-MSC) and umbilical cord (UC-MSC) on neuropathic pain relief
View PaperMesenchymal stem cells or multipotent stromal cells (MSCs) isolated from the bone marrow of adult organisms were initially characterized as plastic adherent, fibroblastoid cells with the capacity to generate heterotopic osseous tissue when transplanted in vivo. In recent years, MSCs or MSClike cells have been shown to reside within the connective tissue of most organs, and their surface phenotype has been well described. A large number of reports have also indicated that the cells possess the capacity to transdifferentiate into epithelial cells and lineages derived from the neuroectoderm. The broad developmental plasticity of MSCs was originally thought to contribute to their demonstrated efficacy in a wide variety of experimental animal models of disease as well as in human clinical trials. However, new findings suggest that the ability of MSCs to alter the tissue microenvironment via secretion of soluble factors may contribute more significantly than their capacity for transdifferentiation in tissue repair. Herein, we critically evaluate the literature describing the plasticity of MSCs and offer insight into how the molecular and functional heterogeneity of this cell population, which reflects the complexity of marrow stroma as an organ system, may confound interpretation of their transdifferentiation potential. Additionally, we argue that this heterogeneity also provides a basis for the broad therapeutic efficacy of MSCs.
View PaperDuring recent years different types of adult stem/progenitor cells have been successfully applied for the treatment of many pathologies, including cardiovascular diseases. The regenerative potential of these cells is considered to be due to their high proliferation and differentiation capacities, paracrine activity, and immunologic privilege. However, therapeutic efficacy of the autologous stem/progenitor cells for most clinical applications remains modest, possibly because of the attenuation of their regenerative potential in aged patients with chronic diseases such as cardiovascular diseases and metabolic disorders. In this review we will discuss the risk factors affecting the therapeutic potential of adult stem/progenitor cells as well as the main approaches to mitigating them using the methods of regenerative medicine.
View PaperAlopecia is caused by a variety of factors which affect the hair cycle and decrease stem cell activity and hair follicle regeneration capability. This process causes lower self-acceptance, which may result in depression and anxiety. However, an early onset of androgenic alopecia is associated with an increased incidence of the metabolic syndrome and an increased risk of the cardiac ischaemic disease. The ubiquity of alopecia provides an encouragement to seek new, more effective therapies aimed at hair follicle regeneration and neoregeneration. We know that stem cells can be used to regenerate hair in several therapeutic strategies: reversing the pathological mechanisms which contribute to hair loss, regeneration of complete hair follicles from their parts, and neogenesis of hair follicles from a stem cell culture with isolated cells or tissue engineering. Hair transplant has become a conventional treatment technique in androgenic alopecia (micrografts). Although an autologous transplant is regarded as the gold standard, its usability is limited, because of both a limited amount of material and a reduced viability of cells obtained in this way. The new therapeutic options are adipose-derived stem cells and stem cells from Wharton’s jelly. They seem an ideal cell population for use in regenerative medicine because of the absence of immunogenic properties and their ease of obtainment, multipotential character, ease of differentiating into various cell lines, and considerable potential for angiogenesis. In this article, we presented advantages and limitations of using these types of cells in alopecia treatment.
View PaperHuman umbilical cord blood mesenchymal stem cells (hUCB-MSCs) are used in tissue repair and regeneration; however, the mechanisms involved are not well understood. We investigated the hair growth-promoting effects of hUCB-MSCs treatment to determine whether hUCB-MSCs enhance the promotion of hair growth. Furthermore, we attempted to identify the factors responsible for hair growth. The effects of hUCB-MSCs on hair growth were investigated in vivo, and hUCB-MSCs advanced anagen onset and hair follicle neogeneration. We found that hUCB-MSCs coculture increased the viability and up-regulated hair induction-related proteins of human dermal papilla cells (hDPCs) in vitro. A growth factor antibody array revealed that secretory factors from hUCB-MSCs are related to hair growth. Insulin-like growth factor binding protein-1 (IGFBP-1) and vascular endothelial growth factor (VEGF) were increased in co-culture medium. Finally, we found that IGFBP-1, through the colocalization of an IGF-1 and IGFBP-1, had positive effects on cell viability; VEGF secretion; expression of alkaline phosphatase (ALP), CD133, and β-catenin; and formation of hDPCs 3D spheroids. Taken together, these data suggest that hUCB-MSCs promote hair growth via a paracrine mechanism.
View PaperStem cells may have potential as a treatment for regenerating hair. Initially, methods to obtain stem cells have concentrated on isolating the primary cells from the tissue of interest through biopsy and growing these cells outside the body to be transplanted into the patient. Stem cell treatment of nonautoimmune hair loss like androgenetic alopecia is promising. Although an autologous transplant is viewed as the standard, its use is limited because of a lack of data and the diminished viability of cells that are made available using this method. Adipose‑derived stem cells are a promising alternative because of their limited immunogenicity. They are easy to obtain, are multipotent, and can differentiate into different cell lines. They also have significant potential for angiogenesis. More studies are needed to establish the efficacy of the various types of stem cell‑based treatments for people with hair loss.
View PaperThe use of stem cells has been reported to improve hair regrowth in several therapeutic strategies, including reversing the pathological mechanisms, that contribute to hair loss, regeneration of hair follicles, or creating hair using the tissue-engineering approach. Although various promising stem cell approaches are progressing via pre-clinical models to clinical trials, intraoperative stem cell treatments with a one-step procedure oer a quicker result by incorporating an autologous cell source without manipulation, which may be injected by surgeons through a well-established clinical practice. Many authors have concentrated on adipose-derived stromal vascular cells due to their ability to separate into numerous cell genealogies, platelet-rich plasma for its ability to enhance cell multiplication and neo-angiogenesis, as well as human follicle mesenchymal stem cells. In this paper, the significant improvements in intraoperative stem cell approaches, from in vivo models to clinical investigations, are reviewed. The potential regenerative instruments and functions of various cell populaces in the hair regrowth process are discussed. The addition of Wnt signaling in dermal papilla cells is considered a key factor in stimulating hair growth. Mesenchymal stem cell-derived signaling and growth factors obtained by platelets influence hair growth through cellular proliferation to prolong the anagen phase (FGF-7), induce cell growth (ERK activation), stimulate hair follicle development (-catenin), and suppress apoptotic cues (Bcl-2 release and Akt activation).
View PaperAlopecia, one of the most common chronic diseases, can seriously affect a patient’s psychosocial life. Dermal papilla (DP) cells serve as essential signaling centers in the regulation of hair growth and regeneration and are associated with crosstalk between autocrine/paracrine factors and the surrounding environment. We previously demonstrated that amniotic fluid–derived mesenchymal stem cell–conditioned medium (AF-MSC-CM) accelerates hair regeneration and growth. The present study describes the effects of overexpression of a reprogramming factor, Nanog, on MSC properties, the paracrine effects on DP cells, and in vivo hair regrowth. First, we examined the in vitro proliferation and lifespan of AF-MSCs overexpressing reprogramming factors, including Oct4, Nanog, and Lin28, alone or in combination. Among these factors, Nanog was identified as a key factor in maintaining the self-renewal capability of AF-MSCs by delaying cellular senescence, increasing the endogenous expression of Oct4 and Sox2, and preserving stemness. Next, we evaluated the paracrine effects of AF-MSCs overexpressing Nanog (AF-N-MSCs) by monitoring secretory molecules related to hair regeneration and growth (IGF, PDGF, bFGF, and Wnt7a) and proliferation of DP cells. In vivo studies revealed that CM derived from AF-N-MSCs (AF-N-CM) accelerated the telogen-to-anagen transition in hair follicles (HFs) and increased HF density. The expression of DP and HF stem cell markers and genes related to hair induction were higher in AF-N-CM than in CM from AF-MSCs (AF-CM). This study suggests that the secretome from autologous MSCs overexpressing Nanog could be an excellent candidate as a powerful anagen inducer and hair growth stimulator for the treatment of alopecia.
View PaperCell-based cartilage repair procedures are becoming more widely available and have shown promising potential to treat a wide range of cartilage lesion types and sizes, particularly in the knee joint. More recently, techniques have evolved from 2-step techniques that use autologous chondrocyte expansion to 1-step techniques that make use of mesenchymal stem cells (MSCs) embedded onto biocompatible scaffolding. Our 1-step technique has been further developed to provide cell-based cartilage repair using MSCs that have the potential to be used in an off-the-shelf manner, without the need for autologous tissue harvest. Precursor MSCs can be isolated in abundance from the Wharton's jelly of umbilical cord tissue. These cells have been shown to have the desired capacity for proliferation, differentiation, and release of trophic factors that make them an excellent candidate for use in the clinical setting to provide cell-based restoration of hyaline-like cartilage. Although allogeneic in nature, these cells stimulate little or no host immune response and can be stored for long periods while maintaining viability. We present a technique of cartilage repair in the knee using Wharton's jellyederived MSCs embedded onto scaffolding and implanted in a minimally invasive fashion using dry arthroscopy.
View PaperPurpose of Review With the rapid and ongoing evolution of regenerative and sports medicine, the use of stem/stromal cells in ligament repair and reconstruction continues to be investigated and grow. The purpose of this review was to assess available methods and formulations for stem/stromal cell augmentation as well as review early pre-clinical and clinical outcomes for these recently emerging techniques
View PaperTo systematically review the available preclinical evidence of adult stem cells as a biological augmentation in the treatment of animal anterior cruciate ligament (ACL) injury. Study Design: Systematic review. Methods: PubMed (MEDLINE) and Embase were searched for the eligible studies. The inclusion criteria were controlled animal trials of adult stem cells used in ACL treatment (repair or reconstruction). Studies of natural ACL healing without intervention, in vitro studies, ex vivo studies, and studies without controls were excluded. Evidence level, methodologic quality, and risk of bias of each included study were identified using previously established tools. Results: Thirteen animal studies were included. Six of 7 studies using bone marrowederived mesenchymal stem (stromal) cells (BMSCs) reported a positive enhancement in histology, biomechanics, and biochemistry within 12 weeks postoperatively. Four studies using ACL-derived vascular stem cells showed a promoting effect in histology, biomechanics, and imaging within 8 weeks postoperatively. Two studies focusing on animal tendon-derived stem cells (TDSCs) and human umbilical cord bloodederived mesenchymal stem cells (hUCB-MSCs) reported promotable effects for the early healing in a small animal ACL model. Conclusions: BMSCs, ACL-derived vascular stem cells, TDSCs, and hUCB-MSCs were shown to enhance the healing of ACL injury during the early phase in small animal models. Clinical Relevance: Results of clinical trials using adult stem cells in ACL treatment are conflicting, and a systematic review of the current best preclinical evidence is crucial to guide further application
View PaperMesenchymal stem cells (MSCs) were, due to their immunomodulatory and pro-angiogenic characteristics, extensively explored as new therapeutic agents in cell-based therapy of uveitis, glaucoma, retinal and ocular surface diseases.
View PaperVisual impairment is a common ailment of the current world population, with more exposure to CCD screens and fluorescent lighting, approximately 285 billion people suffer from this deficiency and 13% of those are considered clinically blind. More common causes for visual impairment include age-related macular degeneration (AMD), glaucoma and diabetic retinopathy (Zhu et al. Molecular Medicine Reports, 2015; Kolb et al. 2007; Machalińska et al. Current Eye Research, 34(9),748–760, 2009) among a few. As cases of retinal and optic nerve diseases rise, it is vital to find a treatment, which has led to investigation of the therapeutic potential of various stem cells types (Bull et al. Investigative Opthalmology& Visual Science, 50(9), 4244, 2009; Bull et al. Investigative Opthalmology & Visual Science, 49(8), 3449, 2008; Yu et al. Biochemical and Biophysical Research Communications, 344(4), 1071-1079, 2006; Na et al. Graefe's Archive for Clinical and Experimental Ophthalmology, 247(4), 503-514, 2008). In previous studies, some of the stem cell variants used include human Muller SCs and bone marrow derived SCs. Some of the regenerative potential characteristics of mesenchymal progenitor stem cells (MSCs) include their multilineage differentiation potential, their immunomodulatory effects, their high proliferative activity, they can be easily cultured in vitro, and finally their potential to synthesize and secrete membrane derived vesicles rich in growth factors, mRNA and miRNAwhich possibly aid in regulation of tissue damage regeneration. These facts alone, explain why MSCs are so widely used in clinical trials, 350 up to date (Switonski, Reproductive Biology, 14(1), 44–50, 2014). Animal studies have demonstrated that sub-retinal transplantation of MSCs delays retinal degeneration and preserves retinal function through trophic response (Inoue et al. Experimental Eye Research, 85(2), 234–241, 2007). Umbilical cord derived MSCs (UC/MSCs) have also been shown to contain neuroprotective features of ganglion cells in rat studies (Zwart et al. Experimental Neurology, 216(2), 439–448, 2009). This review aims to present current MSC therapies in practice, as well as their retinal regeneration potential in animal models, and their innovative prospects for treatment of human retinal diseases.
View PaperThe amniotic membrane (AM) is the inner layer of the fetal membranes and consist of 3 different layers: the epithelium, basement membrane and stroma which further consists of three contiguous but distinct layers: the inner compact layer , middle fibroblast layer and the outermost spongy layer . The AM has been shown to have anti-inflammatory, anti-fibrotic, anti-angiogenic as well as anti-microbial properties. Also because of its transparent structure, lack of immunogenicity and the ability to provide an excellent substrate for growth, migration and adhesion of epithelial corneal and conjunctival cells, it is being used increasingly for ocular surface reconstruction in a variety of ocular pathologies including corneal disorders associated with limbal stem cell deficiency, surgeries for conjunctival reconstruction, as a carrier for ex vivo expansion of limbal epithelial cells, glaucoma surgeries and sceral melts and perforations. However indiscriminate use of human AM needs to be discouraged as complications though infrequent can occur. These include risk of transmission of bacterial, viral or fungal infections to the recipient if the donors are not adequately screened for communicable diseases, if the membrane is not processed under sterile conditions or if storage is improper. Optimal outcomes can be achieved only with meticulous case selection. This review explores the ever expanding ophthalmological indications for the use of human AM.
View PaperThe present study investigated the therapeutic potential and underlying mechanisms of human umbilical cord mesenchymal stem cells (HUCMSCs) on joint cartilage destruction induced by monosodium iodoacetate (MIA) in mice.
View PaperOnce cartilage is damaged, it has limited potential for self-repair. Autologous chondrocyte implantation is an effective treatment, but patients may suffer during cartilage harvesting and the donor-site morbidity may accelerate joint degeneration. Using autologous mesenchymal stem cells (MSCs) derived chondrocytes is another selection, while it also causes some injuring. The umbilical cord, an ecto-embryo tissue may be an ideal source of cells, because of its accessibility, abundant resources, painless procedures for harvesting, and lack of ethical issues. We isolated MSCs from Wharton’s jelly of human umbilical cord (WMSCs), which expressed CD44, CD105 and CD271 but not CD34 and CD45 with flow cytometry analysis. RT-PCR showed not only positive expression of CD90, c-kit, Sca1, SH2 and SH3 but also positive expression of the chondrocyte markers Sox-9 and Col-2A1. WMSCs cultured in high-density in the presence of transforming growth factor b1 and dexamethasone showed cartilage extracellular matrix-secretion and integrated into a thin piece of cell-based membrane. The cell-based thin membrane cultured in rotary cell culture system formed a round, opaque, glistening non-scaffold cartilage-like tissue, larger and condenser than what was formed with conventional pellet culture. Glycosaminoglycan and type II collagen content significantly increased after 3-week culture. The human WMSCs express characteristics of pre-chondrocytes, low immunogenicity and are easy to be obtained with higher purity because there have no hematopoietic cells in Wharton’s jelly, so it may be a new seed cells more suitable for constructing tissue-engineered cartilage.
View PaperThis study aimed to determine the collagen type II (COL2) and SOX9 expression in interleukin growth factor (IGF-1)-induced Wharton’s Jelly mesenchymal stem cells (WJMSCs) and the level of chondrogenic markers in co-culture IGF1-WJMSCs and IL1β-CHON002 as osteoarthritis (OA) cells model.
View PaperRheumatoid arthritis and osteoarthritis are the main diseases that imply an inflammatory process at the joints involving the articular cartilage. Recently, mesenchymal stem cells (MSCs) derived from perinatal tissues were considered good candidates for cellular therapy of musculoskeletal and orthopaedic diseases, since they can differentiate into multiple cell types and are an easily accessible cellular source. Therefore, several protocols exist on the differentiation of mesenchymal stem cells of different origins into osteoblasts and chondrocytes. Another key feature of MSCs is their capacity to modulate the immune system responses in vitro and in vivo. This may have critical outcomes in diseases of the musculoskeletal system where an inflammatory or autoimmune process is at the basis of the main disease.
View PaperOsteoarthritis (OA) is a slowly progressive disease where cartilage of the synovial joint degenerates. It is most common in the elderly where patients experience pain and reduce physical activity. In combination with lack of conventional treatment, patients are often left with no other choices than arthroplasty. Over the last years, multipotent stromal cells have been used in efforts to treat OA. Mesenchymal stem/progenitor cells (MSCs) are stromal cells that can differentiate into bone, fat, and cartilage cells. They reside within bone marrow and fat. MSCs can also be found in synovial joints where they affect the progression of OA. They can be isolated and proliferated in an incubator before being applied in clinical trials. When it comes to treatment, emphasis has hitherto been on autologous MSCs, but allogenic cells from healthy donors are emerging as another source of the cells. The first adaptations of MSCs revolved in the use of cellrich matrix, delivered as invasive surgical procedure, which resulted in production of hyaline cartilage and fibrocartilage. However, the demand for less invasive delivery of cells has prompted the use of direct intraarticular injections, wherein a large amount of suspended cells are implanted in the cartilage defect.
View PaperAs the most common form of joint disorder, osteoarthritis (OA) imposes a tremendous burden on health care systems worldwide. Without effective cure, OA represents a unique opportunity for innovation in therapeutic development. In contrast to traditional treatments based on drugs, proteins, or antibodies, stem cells are poised to revolutionize medicine as they possess the capacity to replace and repair tissues and organs such as osteoarthritic joints. Among different types of stem cells, mesenchymal stem cells (MSCs) are of mesoderm origin and have been shown to generate cells for tissues of the mesoderm lineage, thus, raising the hope for them being used to treat diseases such as OA. However, given their ability to differentiate into other cell types, MSCs have also been tested in treating a myriad of conditions from diabetes to Parkinson’s disease, apparently of the ectoderm and endoderm lineages. There are ongoing debates whether MSCs can differentiate into lineages outside of the mesoderm and consequently their effectiveness in treating conditions from the ectoderm and endoderm lineages. In this review, we discuss the developmental origin of MSCs, their differentiation potential and immunomodulatory effects, as well as their applications in treating OA. We suggest further investigations into new therapies or combination therapies that may provide more effective treatment for bone and joint diseases. Furthermore, cell-based therapy and its associated safety and effectiveness should be carefully evaluated before clinical translation. This review provides updated information on recent approval of clinical trials and related applications of MSCs, and discusses additional efforts on cell-based therapy for treating OA and other joint and bone diseases.
View PaperOsteoarthritis (OA) is a chronic disease of degenerative joints. Mesenchymal stem cells (MSCs) have been used for cartilage regeneration in OA. We investigated the therapeutic potential of human umbilical cord‑derived MSCs (HUCMSCs) with hyaluronic acid (HA) hydrogel transplanted into a porcine OA preclinical model.
View PaperThe hallmark feature of osteoarthritis is the breakdown in the articular cartilage of joints such as the knee and hip. Both animal and human research has consistently shown that corticosteroid injections into normal and degenerated knees accelerate the arthritic process. A summary of the effects of the intraarticular corticosteroids on articular cartilage includes: a decrease of protein and matrix synthesis, matrix hyaline appearance becomes fibrotic, clumping of collagen, alteration in chondrocyte cell shape, chondrocyte cell proliferation inhibited, chondrocyte cytoxicity enhanced, loss of chondrocytes, surface deterioration including edema, pitting, shredding, ulceration and erosions, inhibition of articular cartilage metabolism, articular cartilage necrosis, thinning of articular cartilage, decrease in cartilage growth and repair, formation of articular cartilage cysts, and ultimately articular cartilage destruction.
View PaperOsteoarthritis is a chronic degenerative joint disorder characterized by articular cartilage destruction and osteophyte formation. Chondrocytes in the matrix have a relatively slow turnover rate, and the tissue itself lacks a blood supply to support repair and remodeling. Researchers have evaluated the effectiveness of stem cell therapy and tissue engineering for treating osteoarthritis. All sources of stem cells, including embryonic, induced pluripotent, fetal, and adult stem cells, have potential use in stem cell therapy, which provides a permanent biological solution. Mesenchymal stem cells (MSCs) isolated from bone marrow, adipose tissue, and umbilical cord show considerable promise for use in cartilage repair. MSCs can be sourced from any or all joint tissues and can modulate the immune response. Additionally, MSCs can directly differentiate into chondrocytes under appropriate signal transduction. They also have immunosuppressive and anti-inflammatory paracrine effects. This article reviews the current clinical applications of MSCs and future directions of research in osteoarthritis.
View PaperOsteoarthritis is a leading cause of pain and disability across the world. With an aging population its prevalence is likely to further increase. Current accepted medical treatment strategies are aimed at symptom control rather than disease modification. Surgical options including joint replacement are not without possible significant complications. A growing interest in the area of regenerative medicine, led by an improved understanding of the role of mesenchymal stem cells in tissue homeostasis and repair, has seen recent focused efforts to explore the potential of stem cell therapies in the active management of symptomatic osteoarthritis. Encouragingly, results of pre-clinical and clinical trials have provided initial evidence of efficacy and indicated safety in the therapeutic use of mesenchymal stem cell therapies for the treatment of knee osteoarthritis. This paper explores the pathogenesis of osteoarthritis and how mesenchymal stem cells may play a role in future management strategies of this disabling condition.
View PaperA detailed search of relevant studies was conducted in three databases including Pubmed/ Medline, Cochrane library, and Embase databases, using the following keywords: “rotator cuff” or “Tissue Engineering” AND “stem cell” from inception to January 01, 2019. The standard mean difference (SMD) and 95% confidence interval (CI) for each individual study were extracted from the original studies or calculated based on relevant data and pooled to obtain integrated estimates using random effects modeling.
View PaperDespite the advances in surgical procedures to repair the rotator cuff, there is a high incidence of failure. Biologic approaches, such as growth factor delivery and stem cell and gene therapy, are potential targets for optimization to improve the outcome of rotator cuff therapies and reduce rates of reinjury. This article outlines the current evidence for growth factor and stem cell therapy in tendon healing and the augmentation of rotator cuff repair.
View PaperTendon injuries are significant clinical problems. Current treatments often result in incomplete repair or healing, which may lead to reduced function and rupture. Stem cellbased therapy is a promising intervention for tendon repair. In this article, we attempt to provide a brief overview on the recent progress in the field, current understanding of the underlying mechanisms of the approach, and the potential of stem cell-based therapies beyond cell implantation. We conclude the review by sharing our viewpoints on the challenges, opportunities, and future directions of this approach.
View PaperThe paper presents current evidence on the properties of human umbilical cord-derived mesenchymal stem cells, including origin, proliferative potential, plasticity, stability of karyotype and phenotype, transcriptome, secretome, and immunomodulatory activity. A review of preclinical studies and clinical trials using this cell type is performed. Prospects for the use of mesenchymal stem cells, derived from the umbilical cord, in cell transplantation are associated with the need for specialized biobanking and transplant standardization criteria.
View PaperMesenchymal stem cells (MSCs) are one of the most promising stem cell types due to their availability and relatively simple requirements for in vitro expansion and genetic manipulation. Besides the well-characterized MSCs derived from bone marrow, there is growing evidence suggesting that dental pulp and the umbilical cord matrix both contain a substantial amount of cells having properties similar to those of MSCs. In order to assess the potential of dental pulp-derived MSCs (DPSC) and umbilical cord-derived MSCs (UCSC) in future clinical applications, it is essential to gain more insight into their differentiation capacity and to evaluate the tissues formed by these cells. In the present study, the morphological and ultrastructural characteristics of DPSC and UCSC induced towards osteogenic, adipogenic, and chondrogenic lineages were investigated. Cultured DPSC and UCSC showed a similar expression pattern of antigens characteristic of MSCs including CD105, CD29, CD44, CD146, and STRO-1. Under appropriate culture conditions, both DPSC and UCSC showed chondrogenic and osteogenic potential.
View PaperThis study has assessed the amounts of insulin-like growth factor I (IGF-I), fibroblast growth factor (FGF), transforming growth factor b (TGF-b), platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) and their binding to extracellular matrix components of Wharton’s jelly. Studies were performed on the umbilical cords taken from human newborns delivered by healthy mothers. Wharton’s jelly was separated and submitted to homogenisation and extraction with acetic acid and TriseHCl buffer. The assays of growth factors were carried out with the use of ELISA commercial kits, together with SDS/polyacrylamide gel electrophoresis of tissue extracts followed by Western immunoblotting. Several growth factors, viz. acidic FGF, basic FGF, EGF, IGF-I, PDGF and TGF-b were detected in Wharton’s jelly. The amounts of these factors per gram of tissue vary from about 40 pg (EGF, PDGF) to about 200 ng (IGF-I). The amounts of peptide growth factors calculated per microgram of DNA are distinctly higher in Wharton’s jelly in comparison to the umbilical cord artery. Western blot analysis demonstrated that almost the entire amount of these factors is bound to high molecular weight components. Since the number of cells in Wharton’s jelly is very low and the amounts of extracellular matrix components are very high, it is concluded that the cells are strongly stimulated by peptide growth factors to produce large amounts of collagen and glycosaminoglycans
View PaperThe role of bone marrow-derived mesenchymal stromal cells (BM-MSC) in preventing the incidence and ameliorating the severity of graft-versus-host disease (GvHD) has recently been reported. However, as the collection of BM-MSC is an invasive procedure, more accessible sources of MSC are desirable
View PaperMesenchymal stem cells derived from human umbilical cord Wharton’s jelly (hWJMSCs) became prospective seed cell candidate for tissue engineering and cell-based therapy because of its variety source, easy procurement, robust proliferation, and high purity compared with bone marrow- and adiposederived MSCs. Such neonatal stem cells can be isolated from a variety of extraembryonic tissues and appear to be more primitive and have greater multi-potentiality than their adult counterparts. In this study, we investigated the immune characters of hWJMSCs and its derived cartilage cells (hWJMSC-Cs) by detecting the expression of major histocompatibility complex I/I(MHC-I/II), costimulatory molecules (CD40, CD80 and CD86) and immune inhibitors including human leukocyte antigen G (HLA-G), indoleamine- 2,3-dioxygenase (IDO), and prostaglandin E2 (PGE2). We found that hWJMSCs did not express MHC-II and costimulatory molecules, but moderately expressed MHC-I, and positively expressed immune inhibitors as HLA-G, IDO, PGE2, demonstrating their very low immunogenicity and potential to induce immune tolerance microenvironment in hosts. The results of chondrogenic differentiated hWJMSCs(hWJMSC-Cs) are similar to those of undifferentiated cells, except for the slightly elevated MHC-II and costimulators expression. Additionally, we detected cytokine profile of hWJMSCs through cytokine antibody array and verified by western blot the positive expression of immune suppressionrelated molecules, HGF, VEGF, TGF, and IL-10. Furthermore, to investigate the in vivo immune response of the cells, hWJMSCs-scaffold constructs were implanted into rabbits and rats, and the result showed that hWJMSCs did not elicit immune rejection in the animals. Their intermediate state between adult and embryonic stem cells makes them an ideal candidate for reprogramming to the pluripotent status. Additional studies are necessary to clarify the potential of hWJMSCs to be used in cartilage and other tissue regeneration and cell-based therapies.
View PaperFeasibility, tolerance, and safety of intravenous infusions of allogeneic mesenchymal stem cell (MSC) therapy in lung transplant recipients with bronchiolitis obliterans syndrome (BOS) are not well established. MSCs were manufactured, cryopreserved, transported to our facility, thawed, and infused into nine recipients with moderate BOS (average drop in forced expiratory volume in 1 second was 56.8%63.2% from post-transplant peak) who were refractory to standard therapy and not candidates for retransplant. Cells were viable and sterile prior to infusion. Patients received a single infusion of either 1 (n53), 2 (n53), or 4 (n53) million MSCs per kg. Patients were medically evaluated before; during; and at 24 hours, 1 week, and 1 month after infusion for evidence of infusion-related adverse events and tolerance of therapy. Vital signs, pulmonary function test results, Borg Dyspnea Index, and routine laboratory data were recorded. Vital signs and O2 saturation did not significantly change during or up to 2 hours after MSC infusion. There were no significant changes in gas exchange variables, pulmonary function test results, or laboratory values at 1, 7, and 30 days postinfusion compared with preinfusion values. Infusion of MSCs in patients with BOS was feasible, safe, and well tolerated and did not produce any significant adverse changes in clinical, functional, or laboratory variables during or up to 30 days after infusion. Manufacturing, transport, and administration of intravenous, allogeneic bone marrow derived MSCs in doses from 1 to 4 million MSCs per kg is safe in lung transplant recipients with BOS
View PaperThe human umbilical cord is a promising source of mesenchymal stem cells (HUCMSCs). Unlike bone marrow stem cells, HUCMSCs have a painless collection procedure and faster self-renewal properties. Different derivation protocols may provide different amounts and populations of stem cells. Stem cell populations have also been reported in other compartments of the umbilical cord, such as the cord lining, perivascular tissue, and Wharton’s jelly. HUCMSCs are noncontroversial sources compared to embryonic stem cells. They can differentiate into the three germ layers that promote tissue repair and modulate immune responses and anticancer properties. Thus, they are attractive autologous or allogenic agents for the treatment of malignant and nonmalignant solid and soft cancers. HUCMCs also can be the feeder layer for embryonic stem cells or other pluripotent stem cells. Regarding their therapeutic value, storage banking system and protocols should be established immediately. This review critically evaluates their therapeutic value, challenges, and future directions for their clinical applications
View PaperThe mesenchymal stroma harbors an important population of cells that possess stem cell-like characteristics including self renewal and differentiation capacities and can be derived from a variety of different sources. These multipotent mesenchymal stem cells (MSC) can be found in nearly all tissues and are mostly located in perivascular niches. MSC have migratory abilities and can secrete protective factors and act as a primary matrix for tissue regeneration during inflammation, tissue injuries and certain cancers.
View PaperMesenchymal stem cells (MSCs) can be isolated from umbilical cord Wharton’s jelly (UC-MSC) and UC can be easily obtained, representing a noncontroversial source of MSCs. UC-MSCs are more primitive than other tissue sources. Previous studies showed that UC-MSCs were still viable and were not rejected 4 months after transplantation as xenografts without the need for immune suppression, indicating that they are favorable cell source for transplantation. In this study, UC-MSCs were induced to differentiate into endothelial-like cells and compared with bone marrow (BM)-MSCs for their endothelial differentiation potential.
View PaperFour strains of dental pulp stem cells (DP-MSCs) were isolated from dental pulp tissue fragments adhered to plastic tissue culture dishes. Mesenchymal stem cells derived from umbilical cord tissue (UBC-MSCs) were isolated with the same technique. Bone marrow derived mesenchymal stem cells (BM-MSCs) were isolated from nucleated cells of bone marrow obtained by density gradient centrifugation. Human mesenchymal stem cells from adipose tissue (ATMSCs) were isolated by collagenase digestion. All kinds of MSCs used in this study were cultivated in low glucose DMEM containing 5% or human platelet extract. All stem cell manipulation was performed in GMP conditions. Expression of 15 pluripotent stem cells genes on the level of proteins was measured by Proteome Profiler Human Pluripotent Stem Cell Array. Induction of MSCs to in vitro differentiation to adipocytes, osteoblasts, chondroblasts was achieved by cultivation of cells in appropriate differentiation medium.
View PaperThe human umbilical cord (UC) is an attractive source of mesenchymal stem cells (MSCs) with unique advantages over other MSC sources. They have been isolated from different compartments of the UC but there has been no rigorous comparison to identify the compartment with the best clinical utility. We compared the histology, fresh and cultured cell numbers, morphology, proliferation, viability, stemness characteristics and differentiation potential of cells from the amnion (AM), subamnion (SA), perivascular (PV), Wharton’s jelly (WJ) and mixed cord (MC) of five UCs. The WJ occupied the largest area in the UC from which 4.61 ± 0.57 x 106 /cm fresh cells could be isolated without culture compared to AM, SA, PV and MC that required culture. The WJ and PV had significantly lesser CD40+ non-stem cell contaminants (26-27%) compared to SA, AM and MC (51-70%). Cells from all compartments were proliferative, expressed the typical MSC-CD, HLA, and ESC markers, telomerase, had normal karyotypes and differentiated into adipocyte, chondrocyte and osteocyte lineages. The cells from WJ showed significantly greater CD24+ and CD108+ numbers and fluorescence intensities that discriminate between MSCs and non-stem cell mesenchymal cells, were negative for the fibroblast-specific and activating-proteins (FSP, FAP) and showed greater osteogenic and chondrogenic differentiation potential compared to AM, SA, PV and MC. Cells from the WJ offer the best clinical utility as (i) they have less non-stem cell contaminants (ii) can be generated in large numbers with minimal culture avoiding changes in phenotype, (iii) their derivation is quick and easy to standardize, (iv) they are rich in stemness characteristics and (v) have high differentiation potential. Our results show that when isolating MSCs from the UC, the WJ should be the preferred compartment, and a standardized method of derivation must be used so as to make meaningful comparisons of data between research groups
View PaperIn recent years there seems to be an unbounded interest concerning mesenchymal stem cells (MSCs). This is mainly attributed to their exciting characteristics including long-term ex vivo proliferation, multilineage potential and immunomodulatory properties. In this regard MSCs emerge as attractive candidates for various therapeutic applications. MSCs were originally isolated from the bone marrow (BM) and this population is still considered as the gold standard for MSC applications. Nevertheless the BM has several limitations as source of MSCs, including MSC low frequency in this compartment, the painful isolation procedure and the decline in MSC characteristics with donor's age. Thus, there is accumulating interest in identifying alternative sources for MSCs. To this end MSCs obtained from the Wharton's Jelly (WJ) of umbilical cords (UC) have gained much attention over the last years since they can be easily isolated, without any ethical concerns, from a tissue which is discarded after birth. Furthermore WJ-derived MSCs represent a more primitive population than their adult counterparts, opening new perspectives for cell-based therapies. In this review we will at first give an overview of the biology of WJ-derived UC-MSCs. Then their potential application for the treatment of cancer and immune mediated disorders, such graft versus host disease (GVHD) and systemic lupus erythematosus (SLE) will be discussed, and finally their putative role as feeder layer for ex vivo hematopoietic stem cell (HSC) expansion will be pointed out.
View PaperMesenchymal stem cells (MSCs) are multipotent cells that have the capability of differentiating into adipogenic, osteogenic, chondrogenic, and neural cells. With these multiple capabilities, MSCs have been highly regarded as effective transplantable cell source for regenerative medicine. A large bank of these cells can be found in several regions of the human umbilical cord (hUC) including the umbilical cord lining, the subendothelial layer, the perivascular zone, and most importantly in Wharton’s jelly (WJ). These cells, all umbilical cord-derived MSCs, are very durable, have large loading capacities, and are considered ethical to harvest because the umbilical cord is often considered a waste. These logistical advantages make WJ as appealing source of stem cells for transplant therapy. In particular, WJ is a predominantly good source of cells because MSCs in WJ (WJ-MSC) are maintained in a very early embryological phase and therefore have retained some of the primitive stemness properties. WJ-MSCs can easily differentiate into a plethora of cell types leading to a variety of applications. In addition, WJ-MSCs are slightly easier to harvest compared to other MSCs (such as bone marrow-derived MSCs). The fascinating stemness properties and therapeutic potential of WJ-MSCs provide great promise in many aspects of regenerative medicine and should be considered for further investigations as safe and effective donor cells for transplantation therapy in many debilitating disorders, which are discussed here. We previously reviewed WJ-MSCs therapeutic potential [1] and now provide an update on their recent preclinical and clinical applications.
View PaperRecent years have seen dramatic increases in the techniques used to harvest and isolate human mesenchymal stem cells. As the potential therapeutic aspects of these cells further develop, informative data on the differences in yields between tissue harvest sites and methods will become increasingly valuable. We collected and compared data on cell yields from multiple tissue harvest sites to provide insight into the varying levels of mesenchymal stem cells by tissue and offer primary and alternative tissue types for harvest and clinical application. Methods: The PubMed and Medline databases were searched for articles relating to the harvest, isolation, and quantification of human mesenchymal stem cells. Selected articles were analyzed for relevant data, which were categorized according to tissue site and, if possible, standardized to facilitate comparison between sites. Results: Human mesenchymal stem cell levels in tissue varied widely according to tissue site and harvest method. Yields for adipose tissue ranged from 4,737 cells/mL of tissue to 1,550,000 cells/mL of tissue. Yields for bone marrow ranged from 1 to 30 cells/mL to 317,400 cells/mL. Yields for umbilical cord tissue ranged from 10,000 cells/mL to 4,700,000 cells/cm of umbilical cord. Secondary tissue harvest sites such as placental tissue and synovium yielded results ranging from 1,000 cells/mL to 30,000 cells/mL. Conclusions: Variations in allogeneic mesenchymal stem cell harvest levels from human tissues reflect the evolving nature of the field, patient demographic characteristics, and differences in harvest and isolation techniques. At present,Wharton’s jelly tissue yields the highest concentration of allogeneic mesenchymal stemcells whereas adipose tissue yields the highest levels of autologousmesenchymal stem cells per milliliter of tissue. Clinical Relevance: This comparison of stem cell levels from the literature offers a primer and guide for harvesting mesenchymal stem cells. Larger mesenchymal stem cell yields are more desirable for research and clinical application.
View PaperMany studies have drawn attention to the emerging role of MSC (mesenchymal stem cells) as a promising population supporting new clinical concepts in cellular therapy. However, the sources from which these cells can be isolated are still under discussion. Whereas BM (bone marrow) is presented as the main source of MSC, despite the invasive procedure related to this source, the possibility of isolating sufficient numbers of these cells from UCB (umbilical cord blood) remains controversial. Here, we present the results of experiments aimed at isolating MSC from UCB, BM and UCM (umbilical cord matrix) using different methods of isolation and various culture media that summarize the main procedures and criteria reported in the literature. Whereas isolation of MSC were successful from BM (10:10) and (UCM) (8:8), only one cord blood sample (1:15) gave rise to MSC using various culture media [DMEM (Dulbecco’s modified Eagle’s medium) +5% platelet lysate, DMEM+10% FBS (fetal bovine serum), DMEM+10% human UCB serum, MSCGMj] and different isolation methods [plastic adherence of total MNC (mononuclear cells), CD3+/CD19+/CD14+/CD38+-depleted MNC and CD133+- or LNGFR+- enriched MNC]. MSC from UCM and BM were able to differentiate into adipocytes, osteocytes and hepatocytes. The expansion potential was highest for MSC from UCM. The two cell populations had CD90+/CD73+/CD105+ phenotype with the additional expression of SSEA4 and LNGFR for BM MSC. These results clearly exclude UCB from the list of MSC sources for clinical use and propose instead UCM as a rich, non-invasive and abundant source of MSC.
View PaperDue to their self-renewal capacity, multilineage differentiation potential, paracrine effects, and immunosuppressive properties, mesenchymal stromal cells (MSCs) are an attractive and promising tool for regenerative medicine. MSCs can be isolated from various tissues but despite their common immunophenotypic characteristics and functional properties, source-dependent differences in MSCs properties have recently emerged and lead to different clinical applications. Considered for a long time as a medical waste, umbilical cord appears these days as a promising source of MSCs. Several reports have shown that umbilical cord-derived MSCs are more primitive, proliferative, and immunosuppressive than their adult counterparts. In this review, we aim at synthesizing the differences between umbilical cord MSCs and MSCs from other sources (bone marrow, adipose tissue, periodontal ligament, dental pulp,.) with regard to their proliferation capacity, proteic and transcriptomic profiles, and their secretome involved in their regenerative, homing, and immunomodulatory capacities. Although umbilical cord MSCs are until now not particularly used as an MSC source in clinical practice, accumulating evidence shows that they may have a therapeutic advantage to treat several diseases, especially autoimmune and neurodegenerative diseases.
View PaperThe two most basic properties of mesenchymal stem cells(MSCs)are the capacities to selfrenew indefinitely and differentiate into multiple cells and tissue types. The cells from human umbilical cord Wharton’s Jelly have properties of MSCs and represent a rich source of primitive cells. This study was conducted to explore the possibility of inducing human umbilical cord Wharton’s Jelly-derived MSCs to differentiate into nerve-like cells.
View PaperThe prevalence of nonhealing wounds is predicted to increase due to the growing aging population. Despite the use of novel skin substitutes and wound dressings, poorly vascularized wound niches impair wound repair. Mesenchymal stem cells (MSCs) have been reported to provide paracrine signals to promote wound healing, but the effect of human Wharton’s jelly-derived MSCs (WJ-MSCs) has not yet been described in human normal skin. The aim of this study is to examine the effects of human WJ-MSC paracrine signaling on normal skin fibroblasts in vitro, and in an in vivo preclinical model.
View PaperHuman mesenchymal stem cells (MSCs) are a promising candidate for cell-based transplantation and regenerative medicine therapies. Thus in the present study Wharton’s Jelly Mesenchymal Stem Cells (WJ-MSCs) have been derived from extra embryonic umbilical cord matrix following removal of both arteries and vein. Also, to overcome the clinical limitations posed by fetal bovine serum (FBS) supplementation because of xenogeneic origin of FBS, usual FBS cell culture supplement has been replaced with human platelet lysate (HPL). Apart from general characteristic features of bone marrow-derived MSCs, wharton jelly-derived MSCs have the ability to maintain phenotypic attributes, cell growth kinetics, cell cycle pattern, in vitro multilineage differentiation plasticity, apoptotic pattern, normal karyotype-like intrinsic mesenchymal stem cell properties in long-term in vitro cultures. Moreover, the WJ-MSCs exhibited the in vitro multilineage differentiation capacity by giving rise to differentiated cells of not only mesodermal lineage but also to the cells of ectodermal and endodermal lineage. Also, WJ-MSC did not present any aberrant cell state upon in vivo transplantation in SCID mice and in vitro soft agar assays. The immunomodulatory potential assessed by gene expression levels of immunomodulatory factors upon exposure to inflammatory cytokines in the fetal WJ-MSCs was relatively higher compared to adult bone marrow-derived MSCs. WJMSCs seeded on decellularized amniotic membrane scaffold transplantation on the skin injury of SCID mice model demonstrates that combination of WJ-MSCs and decellularized amniotic membrane scaffold exhibited significantly better wound-healing capabilities, having reduced scar formation with hair growth and improved biomechanical properties of regenerated skin compared to WJ-MSCs alone. Further, our experimental data indicate that indocyanin green (ICG) at optimal concentration can be resourcefully used for labeling of stem cells and in vivo tracking by near infrared fluorescence non-invasive live cell imaging of labelled transplanted cells, thus proving its utility for therapeutic applications.
View PaperMesenchymal stem cells (MSCs) represent an ideal source of autologous cell-based therapy for chronic wounds. Functional characteristics of MSCs may benefit wound healing by exerting their multi-regenerative potential. However, cell ageing resulting from chronic degenerative diseases or donor age could cause inevitable effects on the regenerative abilities of MSCs. A variety of studies have shown the relationship between MSC ageing and age-related dysfunction, but few associate these age-related impacts on MSCs with their ability of repairing chronic wounds, which are common in the elderly population. Here, we discuss the age-associated changes of MSCs and describe the potential impacts onMSC-based therapy for chronic wounds. Furthermore, critical evaluation of the current literatures is necessary for understanding the underlying mechanisms of MSC aging and raising the corresponding concerns on considering their possible use for chronic wound repair.
View PaperErectile dysfunction (ED) continues to be a significant problem for men following radical prostatectomy. We hypothesize that intracavernous injection of BDNFhypersecreting human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) can ameliorate ED in a rat model of cavernous nerve electrocautery injury (CNEI).
View PaperStem cell research has been concentrated on mesenchymal stem (stromal) cells from bone marrow and adipose tissue. Application of both cell types has produced positive effects on erectile function in various animal models of erectile dysfunction. In acute animal models, such as cavernous nerve injury-induced erectile dysfunction and chemically induced Peyronie’s disease, engraftment and differentiation have not been observed, and stem cells are believed to interact with the host tissue in a paracrine fashion, whereas in chronic disease models some evidence suggests both engraftment and paracrine factors may support improved function. Clinical trials are now investigating therapeutic efficacy of cellular therapy, whereas the first safety studies in humans have recently been published.
View PaperStem cells for sexual disorders are steadily being introduced into clinical trials. Two conditions of importance are the main target for this line of treatment, especially when regarding the wide array of translational and basic science highlighting the potential advantages of regenerative therapy: erectile dysfunction (ED) and more recently Peyronie disease (PD). Cellular therapy offers a treatment modality that might reverse disease progression. It would be used in a curative setting, in contrast to other pharmaceutical agents that are currently available.
View PaperThis study investigated the therapeutic effects of MSC-derived exosomes (MSC-Exos) on erectile function in a rat model of cavernous nerve injury (CNI).
View PaperErectile dysfunction (ED) is the most common sexual disorder that men report to healthcare providers, and is the male sexual dysfunction that has been most investigated. Current treatments for ED focus on relieving the symptoms of ED and therefore tend to provide a temporary solution rather than a cure or reversing the cause. Recently, therapies based on stem cells (SCs) have had an increasing attention for their potential to restore erectile function. Preclinical studies showed that these cells might reverse the pathophysiological changes leading to ED, rather than treating the symptoms of ED. This review is intended to provide an overview of contemporary reports on the use of SCs to treat ED.
View PaperErectile dysfunction (ED) is the most common sexual disorder reported by men to their health-care providers and the most investigated male sexual dysfunction. Currently, the treatment of ED focuses on symptomatic relief of ED and therefore tends to provide temporary relief rather than providing a cure or reversing the underlying cause. Recently, stem cell-based therapies have received increasing attention regarding their potential for the recovery of erectile function. Preclinical studies have shown that these cells may reverse pathophysiological changes leading to ED rather than treating the symptom ED.
View PaperErectile dysfunction (ED) following radical prostatectomy (RP) is a result of inadvertent damage to the cavernous nerves that run close to the prostate capsula. The mechanisms behind the development of post-RP ED are increasingly recognized and include cavernosal fibrosis and cavernosal smooth muscle apoptosis, resulting from cavernous nerve degeneration due to neuropraxia. In recent years, cell-based therapies have received increasing attention regarding their potential for recovery of erectile function following cavernous nerve injury (CNI). Multipotent stromal cells (MSCs) are an attractive cell source for this application based on their regenerative potential and their clinical applicability.
View PaperIn the past decades, great interest has been shown in the development of new ther-apies for erectile dysfunction. Stem cell therapy has generated promising results in numerouspreclinical trials in animal models, which is why has led to the development of the first clini-cal trials in humans. The main cause involved in the pathophysiology of erectile dysfunction isvascular damage related to endothelial and neuronal injury. The interest in stem cell therapyis justified by their capability to differentiate into specific damaged tissues, including endothe-lium and nervous tissue, and induction of the host own cell proliferation. Despite the great effort of the many studies carried out to date, knowledge about biological effects, therapeutic efficacy and safety of stem cells therapy for erectile dysfunction is still very limited.
View PaperAs one of the most common complications of diabetes, diabetic neuropathy often causes foot ulcers and even limb amputations. Inspite of continuous development in antidiabetic drugs, there is still no efficient therapy to cure diabetic neuropathy. Diabetic neuropathy shows declined vascularity in peripheral nerves and lack of angiogenic and neurotrophic factors. Mesenchymal stem cells (MSCs) have been indicated as a novel emerging regenerative therapy for diabetic neuropathy because of their multipotency. We will briefly review the pathogenesis of diabetic neuropathy, characteristic of MSCs, effects of MSC therapies for diabetic neuropathy and its related mechanisms. In order to treat diabetic neuropathy, neurotrophic or angiogenic factors in the form of protein or gene therapy are delivered to diabetic neuropathy, but therapeutic efficiencies are very modest if not ineffective. MSC treatment reverses manifestations of diabetic neuropathy. MSCs have an important role to repair tissue and to lower blood glucose level. MSCs even paracrinely secrete neurotrophic factors, angiogenic factors, cytokines, and immunomodulatory substances to ameliorate diabetic neuropathy. There are still several challenges in the clinical translation of MSC therapy, such as safety, optimal dose of administration, optimal mode of cell delivery, issues of MSC heterogeneity, clinically meaningful engraftment, autologous or allogeneic approach, challenges with cell manufacture, and further mechanisms.
View PapertNeuropathy is observed in 50% of diabetic patients with diabetic foot. This study attempted to explore thepotential role of human mesenchymal stem cells-umbilical cord blood (hMSCs-UC) in femoral nerve (FN)neuropathy. The model rats were established by one time administration of streptozotocin and empyro-sis on the dorsal hind foot. At 3d, 7d, 14d after treatment with hMSCs-UC or saline through left femoralartery, the serum NGF was examined by ELISA; NF-200 expression in FN was evaluated by immunohisto-chemistry; the diameter and roundness of FN, the ratio of capillary and muscular fiber of gastrocnemiuswere calculated under light microscope; and neuronal degenerations, such as demyelization, axonal atro-phy, and loose arrangement of nerve fibers, were observed by electronic microscope. The results showedthat, in hMSCs-UC-treated model rats, serum NGF was increased with higher positive rate of NF-200.Although the difference in FN diameters was not established among groups, improvement of round-ness of FN was confirmed with increase in the numbers of capillary in FN-innervated gastrocnemius;additionally, degenerative neuropathy was significantly improved. Importantly, the functional study ofelectroneurogram (ENG) showed that, slowed conduction of FN in model rats was significantly restoredby hMSCs-CU treatment. These data suggested that hMSCs-UC-treatment partially reverse the neuronal degeneration and nerve function of FN, which might be contributed by the upregulation of NGF with dramatic angiogenesis in FN-innervated gastrocnemius, consequently reversing neuronal structure and function, preventing or curing foot ulceration.
View PaperNeuropathic pain induced by injury to the somatosensory system is a great clinical problem. Despite multiple therapeutic strategies, the medical community still faces a challenge to treat neuropathic pain in a complete and definitive way, since the pathogenesis of this hypersensitive state is very complex. Stem cell transplantation may be an important approach for the treatment of neuropathic pain. This article aimed to review important and illustrative results from recent stem cell studies under various neuropathic pain conditions and to interpret their clinical implications for stem cell transplantation.
View PaperThe diabetic foot is a serious complication of diabetes.Mesenchymal stem cells are an abundant source of stem cells which occupy a special position in cell therapies, and recent studies have suggested that mesenchymal stemcells can play essential roles in treatments for the diabetic foot. Here, we discuss the advances that have been made in mesenchymal stem cell treatments for this condition. The roles and functional mechanisms of mesenchymal stem cells in the diabetic foot are also summarized, and insights into current and future studies are presented.
View PaperMesenchymal stem cells (MSCs) from Wharton’s jelly present high plasticity and low immunogenicity, turning them into a desirable form of cell therapy for the injured nervous system. Their isolation, expansion, and characterization have been performed from cryopreserved umbilical cord tissue. Great concern has been dedicated to the collection, preservation, and transport protocols of the umbilical cord after the parturition to the laboratory in order to obtain samples with higher number of viable MSCs without microbiological contamination. Different biomaterials like chitosan-silicate hybrid
View PaperOver the past 20 years, stem cell technologies have become an increasingly attractive option to investigate and treat neurodegenerative diseases. In the current review, we discuss the process of extending basic stem cell research into translational therapies for patients suffering from neurodegenerative diseases. We begin with a discussion on the burden of these diseases on society, emphasizing the need for increased attention towards advancing stem cell therapies. We then explain the various types of stem cells utilized in neurodegenerative disease research, and outline important issues to consider in the transition of stem cell therapy from bench to bedside. Finally, we detail the current progress regarding the applications of stem cell therapies to specific neurodegenerative diseases, focusing on Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and spinal muscular atrophy. With a greater understanding of the capacity of stem cell technologies, there is growing public hope that stem cell therapies will continue to progress into realistic and efficacious treatments for neurodegenerative diseases.
View PaperIn this study, we aim to determine the in vivo effect of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) on neuropathic pain, using three, principal peripheral neuropathic pain models. Four weeks after hUCBMSC transplantation, we observed significant antinociceptive effect in hUCB-MSC– transplanted rats compared to that in the vehicle-treated control. Spinal cord cells positive for c-fos, CGRP, p-ERK, p-p 38, MMP-9 and MMP 2 were significantly decreased in only CCI model of hUCB-MSCs-grafted rats, while spinal cord cells positive for CGRP, p-ERK and MMP-2 significantly decreased in SNL model of hUCBMSCs- grafted rats and spinal cord cells positive for CGRP and MMP-2 significantly decreased in SNI model of hUCB-MSCs-grafted rats, compared to the control 4 weeks or 8weeks after transplantation (p<0.05). However, cells positive for TIMP-2, an endogenous tissue inhibitor of MMP-2, were significantly increased in SNL and SNI models of hUCB-MSCs-grafted rats. Taken together, subcutaneous injection of hUCBMSCs may have an antinociceptive effect via modulation of pain signaling during pain signal processing within the nervous system, especially for CCI model. Thus, subcutaneous administration of hUCB-MSCs might be beneficial for improving those patients suffering from neuropathic pain by decreasing neuropathic pain activation factors, while increasing neuropathic pain inhibition factor.
View PaperSubstantial inconsistencies in mesenchymal stem (stromal) cell (MSC) therapy reported in early translational and clinical studies may indicate need for selection of the proper cell population for any particular therapeutic purpose. In the present study we have examined stromal stem cells derived either from umbilical cord Wharton’s Jelly (WJ-MSC) or bone marrow (BM-MSC) of adult, healthy donors.The cells characterized in accordance with the International Society for Cellular Therapy (ISCT) indications as well as other phenotypic and functional parameters have been compared under strictly controlled culture conditions. WJ-MSC, in comparison with BM-MSC, exhibited a higher proliferation rate, a greater expansion capability being additionally stimulated under low-oxygen atmosphere, enhanced neurotrophic factors gene expression and spontaneous tendency toward a neural lineage differentiation commitment confirmed by protein and gene marker induction. Our data suggest that WJ-MSC may represent an example of immature-type “pre-MSC,” where a substantial cellular component is embryonic-like, pluripotent derivatives with the default neural-like differentiation. These cells may contribute in different extents to nearly all classical MSC populations adversely correlated with the age of cell donors. Our data suggest that neuro-epithelial markers, like nestin, stage specific embryonic antigens-4 or α-smooth muscle actin expressions, may serve as useful indicators of MSC culture neuro-regeneration–associated potency.
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