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

Charles E. Murry, Mark Soonpaa, Hans Reinecke, Hidehiro Nakajima, Hisako O. Nakajima, Michael Rubart-von der Lohe, Kishore B S Pasumarthi, Jiika Ismail Virag, Stephen H. Bartelmez, Veronica Poppa, Gillian Bradford, Joshua D. Dowell, David A. Williams, Loren Field

Research output: Contribution to journalArticle

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

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Hematopoietic Stem Cells
Cardiac Myocytes
Myocardial Infarction
Stem Cells
Phenotype
Genetic Techniques
Transgenes
Muscle Cells
Cicatrix
Regeneration
Hepatocytes
Skeletal Muscle
Endothelial Cells
Bone Marrow
Epithelial Cells
Clinical Trials
Transplants
Neurons
Injections
Wounds and Injuries

ASJC Scopus subject areas

  • General

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Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. / Murry, Charles E.; Soonpaa, Mark; Reinecke, Hans; Nakajima, Hidehiro; Nakajima, Hisako O.; Rubart-von der Lohe, Michael; Pasumarthi, Kishore B S; Virag, Jiika Ismail; Bartelmez, Stephen H.; Poppa, Veronica; Bradford, Gillian; Dowell, Joshua D.; Williams, David A.; Field, Loren.

In: Nature, Vol. 428, No. 6983, 08.04.2004, p. 664-668.

Research output: Contribution to journalArticle

Murry, CE, Soonpaa, M, Reinecke, H, Nakajima, H, Nakajima, HO, Rubart-von der Lohe, M, Pasumarthi, KBS, Virag, JI, Bartelmez, SH, Poppa, V, Bradford, G, Dowell, JD, Williams, DA & Field, L 2004, 'Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts', Nature, vol. 428, no. 6983, pp. 664-668. https://doi.org/10.1038/nature02446
Murry, Charles E. ; Soonpaa, Mark ; Reinecke, Hans ; Nakajima, Hidehiro ; Nakajima, Hisako O. ; Rubart-von der Lohe, Michael ; Pasumarthi, Kishore B S ; Virag, Jiika Ismail ; Bartelmez, Stephen H. ; Poppa, Veronica ; Bradford, Gillian ; Dowell, Joshua D. ; Williams, David A. ; Field, Loren. / Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. In: Nature. 2004 ; Vol. 428, No. 6983. pp. 664-668.
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