BONE MARROW CELLS TRANSDIFFERENTIATE TO CARDIOMYOCYTES WHEN INTRODUCED INTO THE EMBRYONIC HEART

¹ Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina
² Cell Developmental Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania

^* To whom correspondence should be addressed. E-mail: eisenblm{at}musc.edu.

	Abstract

Since rates of cardiomyocyte generation in the embryo are much higher than within the adult, we explored whether the embryonic heart would serve as useful experimental system for examining the myocardial potential of adult stem cells. Previously, we reported the long-term culturing of adult mouse bone marrow produced a cell population that was both highly enriched for macrophages and cardiac competent. In this study, the myocardial potential of this cell population was analyzed in greater detail using the embryonic chick heart as recipient tissue. Esxperiments involving the co-incubation of labeled bone marrow cells with embryonic heart tissue, showed that BM cells incorporated into the myocardium and immunostained for myocyte proteins. RT-PCR analysis demonstrated that the heart tissue induced bone marrow cells to express the differentiated cardiomyocyte marker -cardiac myosin heavy chain. The cardiomyocyte conversion of the bone marrow cells was verified by harvesting donor cells from mice that were genetically labeled with a myocardial-specific -galactosidase reporter. Embryonic hearts exposed to the transgenic bone marrow in culture exhibited significant numbers of -galactosidase-positive cells, indicating the presence of bone marrow-derived cells that had converted to a myocardial phenotype. Furthermore, when transgenic mouse BM cells were injected into living chick embryos, donor cells incorporated into the developing heart and exhibited a myocardial phenotype. Immunofluorescent analysis demonstrated that donor BM cells exhibiting myocyte markers contained only nuclei from mouse cells, indicating that differentiation and not cell fusion was the predominant mechanism for the acquisition of a myocyte phenotype. These data confirm that adult mouse bone marrow contain cells with the ability to form cardiomyocytes. In addition, the predominance of the macrophage phenotype 3 within the donor bone marrow cell population suggests that transdifferentiation of immuneresponse cells may play a role in cellular regeneration in the adult.

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