MCP-3 is a myocardial mesenchymal stem cell homing factor

¹ Department of Biomedical Engineering, Cleveland Clinic Foundation, Cleveland, Ohio
² Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, Ohio
³ Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
⁴ Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland, Ohio
⁵ Departments of Cardiovascular Medicine, Cell Biology, Biomedical Engineering, Cleveland Clinic Foundation, Cleveland, Ohio; Center for Stem Cell and Regenerative Medicine, Cleveland, Ohio

^* To whom correspondence should be addressed. E-mail: pennm{at}ccf.org.

	Abstract

Mesenchymal stem cells (MSC) have received attention for their therapeutic potential in a number of disease states including bone formation, diabetes, stem cell engraftment following marrow transplantation, graft verse host disease, and heart failure. Despite this diverse interest the molecular signals regulating MSC trafficking to sites of injury are unclear. MSC are known to transiently home to the freshly infarcted myocardium. To identify MSC homing factors, we determined chemokine expression pattern as a function of time after MI. We merged these profiles with chemokine receptors expressed on MSC but not cardiac fibroblasts, which do not home following MI. This analysis identified MCP-3 as a potential MSC homing factor. Over-expression of MCP-3 1 month after MI restored MSC homing to the heart. Following serial infusions of MSC cardiac function improved in MCP-3 expressing hearts (88.7%, p<0.001), but not in control hearts (8.6%, p=0.47). MSC engraftment was not associated with differentiation into cardiac myocytes. Rather MSC engraftment appeared to result in recruitment of myofibroblasts and remodeling of the collagen matrix. These data indicate that MCP-3 is an MSC homing factor; local over-expression of MCP-3 recruits MSC to sites of injured tissue and improves cardiac remodeling independent of cardiac myocyte regeneration.