Circulation Research. 2005;96:127-137
Published online before print November 29, 2004, doi: 10.1161/01.RES.0000151843.79801.60
Published online before print November 29, 2004, doi: 10.1161/01.RES.0000151843.79801.60
© 2005 American Heart Association, Inc.
Integrative Physiology |
Bone Marrow Cells Differentiate in Cardiac Cell Lineages After Infarction Independently of Cell Fusion
From the Cardiovascular Research Institute (J.K., M.R., B.W., S.C., T.H., C.B., D.N., E.Z., M.B., B.N.-G., D.T., A.N., F.Q., K.U., A.L., P.A.), Department of Medicine, New York Medical College, Valhalla; and Department of Physiology and Functional Genomics (H.K.), University of Florida Gainesville.
Correspondence to Jan Kajstura, PhD, or Piero Anversa, MD, Cardiovascular Research Institute, Department of Medicine, Vosburgh Pavilion, Rm 302, New York Medical College, Valhalla, NY 10595. E-mail jan_kajstura{at}nymc.edu or piero_anversa@nymc.edu
Recent studies in mice have challenged the ability of bone marrow cells (BMCs) to differentiate into myocytes and coronary vessels. The claim has also been made that BMCs acquire a cell phenotype different from the blood lineages only by fusing with resident cells. Technical problems exist in the induction of myocardial infarction and the successful injection of BMCs in the mouse heart. Similarly, the accurate analysis of the cell populations implicated in the regeneration of the dead tissue is complex and these factors together may account for the negative findings. In this study, we have implemented a simple protocol that can easily be reproduced and have reevaluated whether injection of BMCs restores the infarcted myocardium in mice and whether cell fusion is involved in tissue reconstitution. For this purpose, c-kit–positive BMCs were obtained from male transgenic mice expressing enhanced green fluorescence protein (EGFP). EGFP and the Y-chromosome were used as markers of the progeny of the transplanted cells in the recipient heart. By this approach, we have demonstrated that BMCs, when properly administrated in the infarcted heart, efficiently differentiate into myocytes and coronary vessels with no detectable differentiation into hemopoietic lineages. However, BMCs have no apparent paracrine effect on the growth behavior of the surviving myocardium. Within the infarct, in 10 days, nearly 4.5 million biochemically and morphologically differentiated myocytes together with coronary arterioles and capillary structures were generated independently of cell fusion. In conclusion, BMCs adopt the cardiac cell lineages and have an important therapeutic impact on ischemic heart failure.
Key Words: transdifferentiation • myocardial regeneration • cell fusion
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