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

Ovid Technologies (Wolters Kluwer Health) - Tập 105 Số 1 - Trang 93-98 - 2002
Catalin Toma1, Mark F. Pittenger1, Kevin S. Cahill1, Barry J. Byrne1, Paul Kessler1
1From 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.).

Tóm tắt

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, β-myosin heavy chain, α-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.

Từ khóa


Tài liệu tham khảo

Kao RL Chiu RCJ eds. Cellular Cardiomyoplasty: Myocardial Repair With Cell Implantation. Austin: Landes Bioscience; 1997.

10.1146/annurev.physiol.61.1.219

10.1177/096368979600500113

10.1161/circ.103.14.1920

10.1038/nm0898-929

10.1016/S0140-6736(00)03617-5

10.1016/8756-3282(92)90364-3

10.1126/science.284.5411.143

10.1089/ten.1995.1.327

Gussoni E, Soneoko Y, Strickland C, et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Science. 1999; 401: 390–394.

10.1126/science.279.5356.1528

10.1172/JCI5298

Bittner RE, Schofer C, Weipoltshammer K, et al. Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anat Embryol (Berl). 1999; 5: 391–396.

10.1161/circ.100.suppl_2.Ii-247

10.1067/mtc.2000.110250

10.1016/S0959-437X(96)80066-9

10.1172/JCI1505

Schultheiss TM Lassar AB. Vertebrate heart induction.In: Harvey RP Rosenthal N eds. Heart Development. New York: Academic Press; 1999: 52–64.

Engelmann GL, Campbell SE, Rakusan K. Immediate postnatal rat heart development modified by abdominal aortic banding: analysis of gene expression. Mol Cell Biochem. 1996; 163: 47–56.

10.1016/S0021-9258(18)47123-2

10.1006/dbio.1997.8718

10.1074/jbc.273.17.10261

10.1038/35070587

10.1038/35082631

10.1172/JCI12150

Thông tin
Thông tin xuất bản

Ovid Technologies (Wolters Kluwer Health)

Tập 105 Số 1

93-98

Thông tin tác giả