Immunogenicity of MSCs

MSCs in cell culture. Image by AKB.

Mesenchymal stem cells (MSCs) are adult fibroblast-like cells found in the bone marrow and fat. MSCs produce paracrine factors that modulate immune responses, promote growth of new blood vessels, and stimulate endogenous progenitor cells to form new tissue. These properties make MSCs ideal candidates for new cellular therapies aimed at treating immune-mediated diseases and healing injured tissues.

Autologous therapy, where a patient’s own cells are used, requires a lengthy cell culture process and the efficacy is dependent on the quality of the cells. Ideally, banked allogeneic cells of know quality from a healthy donor would be used in an off-the-shelf manner. Like a transplanted organ, the immune system can recognize foreign or “non-self” MHC molecules on the surface of allogeneic MSCs and kill them thereby limiting the efficacy of the treatment and increasing the risk of adverse effects.

My research involves using transforming growth factor-beta2 (TGF-β2) to downregulate expression of MHC molecules on the surface of MSCs. I am currently investigating whether downregulation of MHC surface molecules enhances the ability of MSCs to evade the recipient immune response and prevent MSC death. I am also interested in how the immune system rejects donor MSCs during inflammation and using this knowledge to make allogeneic MSCs more immune evasive.