Local microenvironment activation™ platform
BioStem's Local Microenvironment Activation™ Platform
Our proprietary approach, called Local MicroEnvironment Activation™ (LMA), uses combinations of small molecules, cytokines, and growth factors (SMCGF) to activate the local microenvironment and create communication for repair in the tissue.
What is a local microenvironment?
The local microenvironment is defined as the immediate environment surrounding a cell, or group of cells, which contains physical and chemical signals that can either directly or indirectly influence cellular behavior. Development, growth and repair of tissue is largely dependent on microenvironmental conditions. Changes in the microenvironment including alterations in mechanical forces, chemokines, extracellular matrix and growth factors directly impact cellular recruitment and activation.
What composes a local microenvironment?
The local microenvironment includes:
- Extracellular matrix
- Similar or dissimilar cells that are in close proximity
- Cytokines, growth factors, extracellular vesicles and small nucleic acids.
- Local physical properties of a tissue
The importance of each individual factor depends on the nature of the cell or tissue. The combination of these factors ultimately influences the behavior of the cells and tissue in the local microenvironment. The nature of the interaction between the local microenvironment and cells is bidirectional. This means that as tissue remodels, it can produce, rearrange, and realign the extracellular matrix components. Similarly, the extracellular matrix itself can regulate and transform the activity of cells.
What is Local Microenvironment Activation (LMA)?
Local microenvironmental activation (LMA), refers to the positive impact that the allograft elicits on the application site's cells and tissues. This activation occurs through several mechanisms:
- Stromal support and scaffolding
- Direct growth factor delivery
- Exosome signaling
Stromal Support and Scaffolding
It is well known in biologics that perinatal tissue allografts are capable of providing the scaffolding for endogenous and introduced cells to connect and develop, which has a beneficial effect on the healing process. The scaffolding may be in the form of micronized tissue offering a physical base for the endogenous cells to interact. It may also be the gelatinous composition of the Wharton's jelly or amniotic fluid which provides a viscosity favored by the tissues for regeneration or healing. The molecules within these scaffolds, such as collagen and fibronectin, promote the foundation for regenerative activity. Introducing these tissue allografts to site of damage elicits a response in the local microenvironment to use them as scaffolding for growth.
Direct growth factor delivery
Upon application, growth factors within the perinatal tissue allograft are immediately available to surrounding cells and tissues. These growth factors bind to receptors on the surrounding cells and local tissue, establishing a signaling cascade within the tissue to begin regenerative activity, initiating an immediate local effect. The LMA concentrates on growth factor ligand concentration (e.g. VEGF, IL-1Ra., HGF) because the receptors are generally on the cells, so providing the receptors is not as effective as providing the ligands.
Also delivered are extracellular vesicles called exosomes, which carry protected RNA, miRNA, and some proteins. The exosomes act as protected packets of information for the local environment. When the packets are bound to the cells within the tissue, they can trigger signaling on the surface of the endogenous cells. Exosomes are also taken up by the tissues (endocytosis) or fused, where they release the regenerative factors required to start development. This signaling cascade is specific to the proteins on the surface of the exosomes. Since the exosomes are from placental sources, the signals they carry are enriched in growth signaling know to be important in wound healing.