Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction

doi:10.1073/pnas.0504388102

Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction

^*Department of Medicine, Cardiology Division, and ^‡Department of Surgery, Division of Cardiac Surgery, The Johns Hopkins Hospital, Blalock 618, 600 North Wolfe Street, Baltimore, MD 21287; ^†Institute for Cell Engineering, Broadway Research Building, Suite 651, 733 North Broadway,The Johns Hopkins University School of Medicine, Baltimore, MD 21205; and ^§Osiris Therapeutics, 2001 Aliceanna Street, Baltimore, MD 21231-3043

Communicated by Victor A. McKusick, The Johns Hopkins University School of Medicine, Baltimore, MD, June 2, 2005 (received for review April 13, 2005)

Abstract

Although clinical trials of autologous whole bone marrow for cardiac repair demonstrate promising results, many practical and mechanistic issues regarding this therapy remain highly controversial. Here, we report the results of a randomized study of bone-marrow-derived mesenchymal stem cells, administered to pigs, which offer several new insights regarding cellular cardiomyoplasty. First, cells were safely injected by using a percutaneous-injection catheter 3 d after myocardial infarction. Second, cellular transplantation resulted in long-term engraftment, profound reduction in scar formation, and near-normalization of cardiac function. Third, transplanted cells were preprepared from an allogeneic donor and were not rejected, a major practical advance for widespread application of this therapy. Together, these findings demonstrate that the direct injection of cellular grafts into damaged myocardium is safe and effective in the periinfarct period. The direct delivery of cells to necrotic myocardium offers a valuable alternative to intracoronary cell injections, and the use of allogeneic mesenchymal stem cells provides a valuable strategy for cardiac regenerative therapy that avoids the need for preparing autologous cells from the recipient.

Footnotes

↵ ∥ To whom correspondence should be addressed. E-mail: jhare{at}mail.jhmi.edu.
↵ ¶ J.Q.K. and B.J.M. are employees of Osiris Therapeutics.
Author contributions: L.C.A., W.W.B., B.J.M., and J.M.H. designed research; L.C.A., A.P.S., K.H.S., M.S.J., J.-S.X., S.C., D.J.D., T.F., G.S., S.L., A.W.H., and J.M.H. performed research; L.C.A., A.P.S., K.H.S., M.S.J., J.-S.X., S.C., D.J.D., J.Q.K., B.J.M., and J.M.H. analyzed data; and L.C.A., A.P.S., and J.M.H. wrote the paper.
Abbreviations: Ees, ventricular elastance, slope of the end-systolic pressure–dimension relationship; LAD, left anterior descending coronary artery; LV, left ventricular; MI, myocardial infarction; MSC, mesenchymal stem cell; MVO₂, myocardial oxygen consumption per cardiac cycle; SW, stroke work.