Multipotent adult progenitor cell transplantation increases vascularity and improves left ventricular function after myocardial infarction

Beatriz Pelacho, Yasuhiro Nakamura, Jianyi Zhang, Jeff Ross, Yves Heremans, Molly Nelson-Holte, Brad Lemke, Julianna Hagenbrock, Yuehua Jiang, Felipe Prosper, Aernout Luttun, Catherine M. Verfaillie

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Progressive contractile dysfunction of viable myocardium that surrounds a large infarct leads to heart failure following acute myocardial infarction (AMI). Experimental evidence indicates that cellular transplantation may improve the left ventricular (LV) contractile performance, even though the underlying mechanisms remain undefined. Here, we compared the effect of transplantation of murine multipotent adult progenitor cells (MAPCs), a population of adult bone marrow-derived cells that differentiate into cells of mesodermal, endodermal and ectodermal origin, with murine bone marrow cells (BMCs) or fibroblasts on post-infarct cardiac function by peri-infarct injection after coronary artery ligation in mice. We demonstrate that, in contrast to the other cell populations, transplantation of MAPCs significantly improved LV contractile function for at least 8 weeks posttransplantation and, although BMCs reduced infarct size, the decrease in scar size was substantially greater in MAPC-treated hearts. As neither MAPCs nor BMCs were present beyond 1 week, the beneficial effect was not due to differentiation and direct contribution of MAPCs to the vascular or cardiomyocyte compartment. Significantly more inflammatory cells were present in MAPC- than BMC-treated hearts at 1 week, which was accompanied by increased vascularity 8 weeks posttransplantation. We hypothesize that MAPCs indirectly contributed to these effects, by secreting inflammatory [monocyte chemoattractant protein-1 (MCP)-1], and vascular growth factors [vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-BB, and transforming growth factor (TGF)β1), and others, resulting in increased angiogenensis and cardioprotection.

Original languageEnglish (US)
Pages (from-to)51-59
Number of pages9
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume1
Issue number1
DOIs
StatePublished - Jan 2007

Keywords

  • Acute myocardial infarction
  • Adult stem cells
  • Angiogenesis
  • Bone marrow
  • Cellular therapy

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