ZWEIG BANNER  

The Harry M. Zweig Memorial Fund for Equine Research


Macrophage Regulation of Mesenchymal Stem Cell Function in Tissue

Principal Investigator: Lisa Fortier
Contact Information: Email: laf4@cornell.edu; Phone: 607-253-3102
Project Costs: $63,887
Project Period: 1/1/2016-12/31/2016

Dr. Lisa Fortier
Dr. Lisa Fortier

Mesenchymal stem cells (MSCs) have the therapeutic potential to treat a wide variety of inflammatory and degenerative disease processes; however, little is known about how the recipient environment, the injured tissue into which the stem cells are delivered, affects the identity and function of the transplanted MSCs.

Although MSCs can turn into many cell types of many tissues including joint, muscle, and nerve, contemporary evidence suggests that the regenerative effects of MSCs are through their ability to effectively improve the local environment rather than to serve as a cell source for new tissue. MSCs secrete numerous factors thought to produce the therapeutic effect through modulation of the injury reparative process and decreasing the immune reaction at the level of the local environment. Several studies have investigated how transplanted MSCs affect the injured recipient environment, but a large knowledge gap remains concerning the recipient environment effects on MSC function. In this proposal, we will determine how the environment regulates MSC identity, and the functional ability of MSCS to decrease the detrimental effects of inflammatory cells present in the damaged tissue targeted for therapeutic MSCs transplantation.

This proposal has direct clinical implications because depending on the environment where they are residing, or into which they are implanted, MSCs can increase or decrease inflammation. In the body, signals from the damaged tissue environment regulate the response of macrophages, which are white blood cells naturally found in injured tissue sites that can facilitate tissue repair or inflammation. MSCs can elicit changes in macrophage function in damaged tissue, but it is not understood how macrophages impact the function of MSCs. In disease states where inflammatory macrophages predominate, such as in an osteoarthritic joint or inflamed tissue such as a tendon, ligament, or muscle, signals secreted from those macrophages have the potential to change the function transplanted MSC from regenerative to pro-inflammatory.  If pro-inflammatory macrophages alter transplanted MSC function, a further inflammatory reaction could be elicited rather than the intended regenerative effect. To harness the full capacity of MSCs for regenerative medicine approaches, an understanding of how the transplantation/recipient environment affects MSC function is critical.