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(Circulation. 2008;118:S121-S129.)
© 2008 American Heart Association, Inc.

Cell Transplantation and Tissue Regeneration

Comparison of Different Adult Stem Cell Types for Treatment of Myocardial Ischemia

Koen E.A. van der Bogt, MD; Ahmad Y. Sheikh, MD; Sonja Schrepfer, MD, PhD; Grant Hoyt, BS; Feng Cao, MD, PhD; Katherine J. Ransohoff; Rutger-Jan Swijnenburg, MD; Jeremy Pearl, BS; Andrew Lee, BS; Michael Fischbein, MD; Christopher H. Contag, PhD; Robert C. Robbins, MD; Joseph C. Wu, MD, PhD

From the Laboratory of Cardiothoracic Transplantation (K.E.A.v.d.B., A.Y.S., S.S., G.H., K.J.R., R.J.S., J.P., M.F., R.C.R.), the Molecular Imaging Program at Stanford (MIPS) (K.E.A.v.d.B., F.C., R.J.S., A.L., J.C.W.), the Department of Pediatrics (C.H.C.), and the Department of Medicine, Division of Cardiology (J.C.W.), Stanford University School of Medicine, Stanford, Calif; and the Department of Surgery (K.E.A.v.d.B., R.J.S.), Leiden University Medical Center, Leiden, The Netherlands.

Correspondence to Joseph C. Wu, MD, PhD, 300 Pasteur Drive, Edwards Building R-354, Stanford, CA 94305-5324. E-mail joewu{at}stanford.edu

Background— A comparative analysis of the efficacy of different cell candidates for the treatment of heart disease remains to be described. This study is designed to evaluate the therapeutic efficacy of 4 cell types in a murine model of myocardial infarction.

Methods and Results— Bone marrow mononuclear cells (MN), mesenchymal stem cells (MSC), skeletal myoblasts (SkMb), and fibroblasts (Fibro) expressing firefly luciferase (Fluc) and green fluorescence protein (GFP) were characterized by flow cytometry, bioluminescence imaging (BLI), and luminometry. Female FVB mice (n=70) underwent LAD ligation and intramyocardially received one cell type (5x10⁵) or PBS. Cell survival was measured by BLI and by TaqMan PCR. Cardiac function was assessed by echocardiography and invasive hemodynamic measurements. Fluc expression correlated with cell number in all groups (r²>0.93). In vivo BLI revealed acute donor cell death of MSC, SkMb, and Fibro within 3 weeks after transplantation. By contrast, cardiac signals were still present after 6 weeks in the MN group, as confirmed by TaqMan PCR (P<0.01). Echocardiography showed significant preservation of fractional shortening in the MN group compared to controls (P<0.05). Measurements of left ventricular end-systolic/diastolic volumes revealed that the least amount of ventricular dilatation occurred in the MN group (P<0.05). Histology confirmed the presence of MN, although there was no evidence of transdifferentiation by donor MN into cardiomyocytes.

Conclusions— This is the first study to show that compared to MSC, SkMB, and Fibro, MN exhibit a more favorable survival pattern, which translates into a more robust preservation of cardiac function.

Key Words: myocardial infarction • molecular imaging • bone marrow stem cells • mesenchymal stem cells • skeletal myoblasts

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