Xenotransplant cardiac chimera: immune tolerance of adult stem cells

Background. Bone marrow stromal cells have been shown to engraft into xenogeneic fetal recipients. In view of the potential clinical utility as an alternative source for cellular and gene therapies, we studied the fate of xenogeneic marrow stromal cells after their systemic transplantation into fully immunocompetent adult recipients without immunosuppression. Methods. Bone marrow stromal cells were isolated from C57B1/6 mice and retrovirally transduced with LacZ reporter gene for cell labeling. We then injected 6 × 106 labeled cells into immunocompetent adult Lewis rats. One week later, the recipient animals underwent coronary artery ligation and were sacrificed at various time points ranging from 1 day to 12 weeks after ligation. Hearts, blood, and bone marrow samples were collected for histologic and immunohistochemical studies. Results. Labeled mice cells engrafted into the bone marrow cavities of the recipient rats for at least 13 weeks after transplantation without any immunosuppression. On the other hand, circulating mice cells were positive only for the animals with 1-day-old myocardial infarction. At various time points, numerous mice cells could be found in the infarcted myocardium that were not seen before coronary ligation. Some of these cells subsequently showed positive staining for cardiomyocyte specific proteins, while other labeled cells participated in angiogenesis in the infarcted area. Conclusions. The marrow stromal cells are adult stem cells with unique immunologic tolerance allowing their engraftment into a xenogeneic environment, while preserving their ability to be recruited to an injured myocardium by way of the bloodstream and to undergo differentiation to form a stable cardiac chimera.