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.

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C.E.M. and L.J.F. thank L. Reinlib for his longstanding support of this collaboration. We thank C. Storey for assistance in sorting HSCs and in bone marrow transplantation, and L. Fernando Santana for assistance with enzymatic dissociation of mouse hearts. These studies were supported in part by NIH grants to C.E.M. and L.J.F., and by the HHMI (G.B., D.A.W.).

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Author notes

    • Kishore B. S. Pasumarthi
    •  & David A. Williams

    Present addresses: Department of Pharmacology Dalhousie University, Sir Charles Tupper Medical Bldg, Room 6-F1, 5850 College Street, Halifax B3H 1X5, Canada (K.B.S.P.); Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039, USA (D.A.W.)


  1. Department of Pathology, Box 357470, Room D-514 HSB, University of Washington, Seattle, Washington 98195, USA

    • Charles E. Murry
    • , Hans Reinecke
    • , Jitka Ismail Virag
    •  & Veronica Poppa
  2. Wells Center for Pediatric Research, Indiana University, 1044 West Walnut Street, R4 Bldg, Room W376, Indianapolis 46202-5225, USA

    • Mark H. Soonpaa
    • , Hidehiro Nakajima
    • , Hisako O. Nakajima
    • , Michael Rubart
    • , Kishore B. S. Pasumarthi
    • , Gillian Bradford
    • , Joshua D. Dowell
    • , David A. Williams
    •  & Loren J. Field
  3. Department of Pathobiology, University of Washington, Seattle, Washington 98195, USA

    • Stephen H. Bartelmez


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Competing interests

The laboratory of C.E.M. receives partial research funding from Geron. L.J.F. is a consultant for Cardion.

Corresponding author

Correspondence to Charles E. Murry.

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    Supplementary Information

    Includes supplementary table showing methodological comparison of Orlic et al. vs. Murry et al. and supplementary methods.

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