Abstract 2039: Marrow Stromal Cells As “Universal Donor Cells” For Myocardial Regenerative Therapy: Their Unique Immune Tolerance
Introduction: Recently rodent and porcine bone marrow stromal cells (MSC) have been reported to be uniquely immune tolerant, both in the in vitro mixed lymphocyte co-culture studies and in the in vivo allo- and xeno-transplant models. In order to confirm these findings in human cells, we tested the hypothesis that human MSCs are also immune tolerant, such that they can be useful as “universal donor cells” for myocardial regenerative therapy.
Methods: Immunocompetent female Lewis rats underwent left coronary artery ligations and were randomized into 3 groups. In group I (n=40), lac-Z labeled male human MSCs (3x106 cells) characterized with specific cell surface markers, were implanted into the peri-infarcted area. In group II and III (n=10/group), isogenic rat MSCs or cell-free medium were injected respectively. Echocardiography was carried out to assess cardiac function, and the heart specimens were examined serially for up to 8 weeks with immunohistochemistry and PCR to assess MSC survival and differentiation.
Results: In groups I and II, human and rat MSCs were found histologically to survive within the rat myocardium without immunosuppression. This was confirmed by PCR. No cellular infiltration characteristic of immune rejection was noted. Some of these cells appeared to express cardiomyocyte markers such as troponin-Ic and connexin 43. Furthermore, a significant increase in the ejection fraction from 35.2%±5.5% to 43.8%±6.1% (P<0.001), and in fractional shortening (15.1%±2.8% to 17.4%±3.6%; P=0.04) were noted in group I. Similar changes were observed in group II. In contrast, there was a reduction in the ejection fraction (36.7%±4.1% to 25.6%±5.7%; P=0.002) and fractional shortening (14.7%±2.1% to 9.5%±1.1%; P=0.002), as well as a progressive worsening in the LV dimensions in group III.
Conclusions: Human MSC survived in this xenotransplant environment and contributed to the significant improvement in the overall cardiac function. Our findings support the feasibility of using MSCs as “universal donor cells” for xeno- or allo-geneic cell therapy, as they can be prepared and stored well in advance for urgent use. Allogeneic MSCs from healthy donors may be particularly useful for severely ill or elderly patients whose own MSCs may be dysfunctional.