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(Circulation. 2002;105:93.)
© 2002 American Heart Association, Inc.

Basic Science Reports

Human Mesenchymal Stem Cells Differentiate to a Cardiomyocyte Phenotype in the Adult Murine Heart

Catalin Toma, MD; Mark F. Pittenger, PhD; Kevin S. Cahill, BS; Barry J. Byrne, MD, PhD; Paul D. Kessler, MD

From the Department of Medicine, Division of Cardiology, Johns Hopkins School of Medicine (C.T., P.D.K.), and Osiris Therapeutics, Inc (M.F.P.), Baltimore, Md; and the Powell Gene Therapy Center, Departments of Pediatrics, Molecular Genetics, and Microbiology, University of Florida School of Medicine, Gainesville, Fla (K.S.C., B.J.B.).

Correspondence to Mark Pittenger, PhD, Osiris Therapeutics Inc, 2001 Aliceanna St, Baltimore, MD 21231. E-mail mpittenger{at}osiristx.com

Background— Cellular cardiomyoplasty has been proposed as an alternative strategy for augmenting the function of diseased myocardium. We investigated the potential of human mesenchymal stem cells (hMSCs) from adult bone marrow to undergo myogenic differentiation once transplanted into the adult murine myocardium.

Methods and Results— A small bone marrow aspirate was taken from the iliac crest of healthy human volunteers, and hMSCs were isolated as previously described. The stem cells, labeled with lacZ, were injected into the left ventricle of CB17 SCID/beige adult mice. At 4 days after injection, none of the engrafted hMSCs expressed myogenic markers. A limited number of cells survived past 1 week and over time morphologically resembled the surrounding host cardiomyocytes. Immunohistochemistry revealed de novo expression of desmin, ß-myosin heavy chain, -actinin, cardiac troponin T, and phospholamban at levels comparable to those of the host cardiomyocytes; sarcomeric organization of the contractile proteins was observed. In comparison, neither cardiac troponin T nor phospholamban was detected in the myotubes formed in vitro by MyoD-transduced hMSCs.

Conclusions— The purified hMSCs from adult bone marrow engrafted in the myocardium appeared to differentiate into cardiomyocytes. The persistence of the engrafted hMSCs and their in situ differentiation in the heart may represent the basis for using these adult stem cells for cellular cardiomyoplasty.

Key Words: stem cells • genes • myocytes • heart failure

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