At the heart of the Vitalgenics Stem Cell programs is the innovative use of a unique set of cells called Mesenchymal Stem Cells (MSCs). Just like all stem cells, MSCs are also multipotent and can be isolated from a number of sources. Though a popular source of MSCs is bone marrow, Vitalgenics prefers to use MSCs derived from umbilical cord (UC) blood.

When speaking about MSCs in general terms, there are some very fascinating characteristics they exhibit that are important to learn and understand for every practitioner and patient.

Some unique attributes of UC-MSCs are:

• Ability to accumulate in damaged tissue or inflamed regions of the body – also known as their ‘homing mechanism’
• Exhibit faster self-renewal and differentiation into three germ layers and signalling other tissues and cells nearby (paracrine effects)
• Directly promote tissue repair and Immunomodulation

The homing mechanism of Mesenchymal Stem Cells (MSCs) lies in their ability to reach the damaged tissue in response to a correct combination of signaling molecules from the injured tissue and corresponding receptors on the MSCs themselves. Most evidence of migration and homing mechanisms has derived from studies evaluating leucocyte migration into inflamed tissues. Despite a considerable body of literature reporting the mechanism of MSC migration toward injured tissue and the role of surface receptors and molecules that drive this migration, the mechanisms by which MSCs are recruited are not fully understood.

Studies performed both in human and animal models demonstrated that MSCs migrate specifically to damaged tissue sites exhibiting inflammation, although most became trapped in the microvasculature of the lung. MSC homing involves several important cell trafficking-related molecules such as chemokines, adhesion molecules, and matrix metalloproteinases (MMPs). Among them, the most important signalers are stromal-derived factor 1 (SDF-1), C-X-C chemokine receptor type 4 (CXCR4), and hepatocyte growth factor (HGF)-MET proto-oncogene, receptor tyrosine kinase (c-MET) axes. The migration process is highly dependent on the chemokine receptor CXCR4 and its binding partner, the SDF-1 CXCL12, which was previously linked to the homing of hematopoietic stem cells (HSCs). To reach the injured tissue, MSCs first adhere to vascular endothelial cells and cross the endothelial barrier in a process known as transendothelial migration. Studies investigating the mechanisms of adhesion between MSCs and microvascular endothelium indicate that MSCs display coordinated rolling and adhesion behavior on endothelial cells mediated by the very late antigen-4/vascular cell adhesion molecule-1 (VLA-4/VCAM-1).

In addition to chemokines and adhesion molecules, several MMPs such as MMP-2 and membrane type 1 MMP (MT1-MMP) have proven to be essential to the invasiveness of MSCs. Notably, homing-related molecules, in general, can be upregulated by inflammatory cytokines such as tumor necrosis factor (TNF) and IL-1, suggesting that different inflammation statuses might promote distinct MSC engraftment and therapeutic efficiencies.

Since the ability of Mesenchymal Stem Cells (MSCs) to modulate the immune system was first demonstrated in 2000, a body of related literature has revealed that these cells were effective in treating various immune disorders in both human and animal models. Though the mechanism by which these cells exert their immunomodulatory function is not fully understood, the most accredited theory posits cell-to-cell contact and/or the release of soluble immunosuppressive factors. Both in vitro and in vivo studies have reported that MSCs interacted with a wide range of immune cells and displayed an ability to suppress the excessive response of T cells, B cells, dendritic cells, macrophages, and natural killer cells. MSCs can also induce regulatory T cells (Tregs) and maintain the capability of Tregs to suppress self-reactive T-effector responses. It has been proposed that Tregs generated in vivo in the presence of MSCs would persist and expand. Given that injection of exogenous, short-lived MSCs could act as catalysts in expanding long-lasting antigen-specific Tregs, it would have important implications for their immunoregulatory potential.

This evidence has contributed to upholding MSCs as suitable candidates in the treatment of autoimmune diseases and GVHD. For instance, donor-derived MSCs have been shown to induce long-term allograft acceptance in a rat model of heart transplantation. Furthermore, given that inflammation-causative tissue damage is a key process triggered in response to injury and disease, MSCs could become the gold standard for the treatment of any tissue or organ damage associated with intense inflammatory activity (e.g., rheumatoid arthritis, kidney failure, heart injury). According to these findings, it has been proposed that MSCs could play a positive role in promoting tissue repair.

An emerging body of evidence clarifies that the immunomodulatory property of MSCs is not strictly related to immunosuppression. More specifically, it has been proposed that MSCs interact with their environments both by negatively regulating the immune response in the case of major inflammation and by stimulating the immune system by releasing proinflammatory molecules if the level of inflammatory cytokines is low.

The benefits of Mesenchymal Stem Cell (MSC) transplants are attributable to the capacity of MSCs to secrete a wide variety of cytokines, chemokines, and growth factors. Several findings suggest that the key role of MSCs in interacting with their microenvironments involves their release of dozens of active biological factors that exert profound effects on local cellular dynamics. It has also been demonstrated that these released factors may prevent adjacent cells from undergoing apoptosis and stimulate their proliferation, thereby promoting the regeneration of injured tissue.

In regenerative medicine, the paracrine effect exerted by MSCs has been hypothesized to sustain the observation of many scientists reporting that the number of implanted MSCs detected in target tissue was too low to explain tissue recovery or wound healing. Further evidence has clearly demonstrated that infused MSCs, once in damaged tissue sites ripe for repair, interacted closely with local stimuli, including inflammatory cytokines, ligands of toll-like receptors, and hypoxia, which seemed, in turn, to stimulate the cells to show several growth factors that perform multiple functions in tissue regeneration.