Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts

Charles E. Murry (), Mark H. Soonpaa, Hans Reinecke, Hidehiro Nakajima, Hisako O. Nakajima, Michael Rubart, Kishore B. S. Pasumarthi, Jitka Ismail Virag, Stephen H. Bartelmez, Veronica Poppa, Gillian Bradford, Joshua D. Dowell, David A. Williams and Loren J. Field
Additional contact information
Charles E. Murry: University of Washington
Mark H. Soonpaa: Indiana University
Hans Reinecke: University of Washington
Hidehiro Nakajima: Indiana University
Hisako O. Nakajima: Indiana University
Michael Rubart: Indiana University
Kishore B. S. Pasumarthi: Indiana University
Jitka Ismail Virag: University of Washington
Stephen H. Bartelmez: University of Washington
Veronica Poppa: University of Washington
Gillian Bradford: Indiana University
Joshua D. Dowell: Indiana University
David A. Williams: Indiana University
Loren J. Field: Indiana University

Nature, 2004, vol. 428, issue 6983, 664-668

Abstract: Abstract The mammalian heart has a very limited regenerative capacity and, hence, heals by scar formation1. Recent reports suggest that haematopoietic stem cells can transdifferentiate into unexpected phenotypes such as skeletal muscle2,3, hepatocytes4, epithelial cells5, neurons6,7, endothelial cells8 and cardiomyocytes8,9, in response to tissue injury or placement in a new environment. Furthermore, transplanted human hearts contain myocytes derived from extra-cardiac progenitor cells10,11,12, which may have originated from bone marrow8,13,14,15. Although most studies suggest that transdifferentiation is extremely rare under physiological conditions, extensive regeneration of myocardial infarcts was reported recently after direct stem cell injection9, prompting several clinical trials16,17. Here, we used both cardiomyocyte-restricted and ubiquitously expressed reporter transgenes to track the fate of haematopoietic stem cells after 145 transplants into normal and injured adult mouse hearts. No transdifferentiation into cardiomyocytes was detectable when using these genetic techniques to follow cell fate, and stem-cell-engrafted hearts showed no overt increase in cardiomyocytes compared to sham-engrafted hearts. These results indicate that haematopoietic stem cells do not readily acquire a cardiac phenotype, and raise a cautionary note for clinical studies of infarct repair.

Date: 2004
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DOI: 10.1038/nature02446

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