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(Circulation. 2005;112:214-223.)
© 2005 American Heart Association, Inc.

Molecular Cardiology

Allogeneic Mesenchymal Stem Cell Transplantation in Postinfarcted Rat Myocardium

Short- and Long-Term Effects

Wangde Dai, MD; Sharon L. Hale, BS; Bradley J. Martin, PhD; Jin-Qiang Kuang, MS; Joan S. Dow, BS; Loren E. Wold, PhD; Robert A. Kloner, MD, PhD

From The Heart Institute (W.D., S.L.H., J.S.D., L.E.W., R.A.K.), Good Samaritan Hospital, Division of Cardiovascular Medicine of Keck School of Medicine at University of Southern California, Los Angeles, Calif, and Osiris Therapeutics Inc, (B.J.M., J.-Q.K.), Baltimore, Md.

Correspondence to Robert A. Kloner, The Heart Institute, Good Samaritan Hospital, 1225 Wilshire Blvd, Los Angeles, CA 90017. E-mail Rkloner{at}goodsam.org

Received December 7, 2004; revision received March 3, 2005; accepted March 15, 2005.

Background— Mesenchymal stem cells (MSCs) have the potential to replace infarct scar, but the long-term effects are unknown. We studied short- and long-term effects of MSC transplantation on left ventricular (LV) function in a rat myocardial infarction model.

Methods and Results— Saline (n=46) or MSCs labeled with 1,1'-dioctadecyl-3,3,3'3'-testramethylindocarbocyanine perchlorate (DiI; n=49, 2x10⁶ cells each) were injected into the scar of a 1-week-old myocardial infarction in Fischer rats. The presence and differentiation of engrafted cells and their effect on LV ejection fraction was assessed. At 4 weeks, LV stroke volume was significantly greater in the MSC-treated group (145±9 µL) than in the saline group (122±3 µL, P=0.032), and LV ejection fraction was significantly greater in MSC-treated animals (43.8±1.0%) than in the saline group (38.8±1.1%, P=0.0027). However, at 6 months, these benefits of MSC treatment were lost. DiI-positive cells were observed in the MSC group at 2 weeks and at 3 and 6 months. Expression of the muscle-specific markers -actinin, myosin heavy chain, phospholamban, and tropomyosin was not observed at 2 weeks in DiI-positive cells. At 3 and 6 months, the DiI-positive cells were observed to express the above muscle-specific markers, but they did not fully evolve into an adult cardiac phenotype. Some of the DiI-positive cells expressed von Willebrand factor.

Conclusions— Allogeneic MSCs survive in infarcted myocardium as long as 6 months and express markers that suggest muscle and endothelium phenotypes. MSCs improved global LV function at 4 weeks; however, this benefit was transient, which suggests a possible early paracrine effect.

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