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, Jiika Ismail Virag, Stephen H. Bartelmez, Veronica Poppa, Gillian Bradford, Joshua D. Dowell, David A. Williams, Loren J. Field

Research output: Contribution to journalArticle

1809 Scopus citations

Abstract

The mammalian heart has a very limited regenerative capacity and, hence, heals by scar formation. Recent reports suggest that haematopoietic stem cells can transdifferentiate into unexpected phenotypes such as skeletal muscle, hepatocytes, epithelial cells, neurons, endothelial cells and cardiomyocytes, in response to tissue injury or placement in a new environment. Furthermore, transplanted human hearts contain myocytes derived from extra-cardiac progenitor cells, which may have originated from bone marrow. Although most studies suggest that transdifferentiation is extremely rare under physiological conditions, extensive regeneration of myocardial infarcts was reported recently after direct stem cell injection, prompting several clinical trials. 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.

Original languageEnglish (US)
Pages (from-to)664-668
Number of pages5
JournalNature
Volume428
Issue number6983
DOIs
StatePublished - Apr 8 2004

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts'. Together they form a unique fingerprint.

  • Cite this

    Murry, C. E., Soonpaa, M. H., Reinecke, H., Nakajima, H., Nakajima, H. O., Rubart, M., Pasumarthi, K. B. S., Virag, J. I., Bartelmez, S. H., Poppa, V., Bradford, G., Dowell, J. D., Williams, D. A., & Field, L. J. (2004). Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature, 428(6983), 664-668. https://doi.org/10.1038/nature02446