Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling

Ryota Uemura, Meifeng Xu, Nauman Ahmad, Muhammad Ashraf

Research output: Contribution to journalArticle

504 Scopus citations

Abstract

In this study, we hypothesized that bone marrow stem cells (BMSCs) protect ischemic myocardium through paracrine effects that can be further augmented with preconditioning. In in vitro experiments, cell survival factors such as Akt and eNOS were significantly increased in BMSCs following anoxia. In the second series of experiments following coronary ligation in mice, left ventricles were randomly injected with the following: DMEM (G-1), BMSCs (G-2), and preconditioned BMSCs (G-3). Four days after myocardial infarction, BMSCs were observed within injured myocardium in G-2 and G-3. Apoptotic cardiomyocytes within periinfarct area were significantly reduced in G-3. Four weeks after myocardial infarction, smaller left ventricular (LV) dimension and increased LV ejection fraction were observed in G-3. Infarct area was significantly reduced in G-3. However, GFP cardiomyocytes were observed in low numbers within periinfarct area in G-2 and G-3. In conclusion, BMSCs secreted cell survival factors under ischemia, and they prevented apoptosis in cardiomyocytes adjacent to the infarcted area. Preconditioning of BMSCs enhanced their survival and ability to attenuate LV remodeling, which was attributable, in part, to paracrine effects.

Original languageEnglish (US)
Pages (from-to)1414-1421
Number of pages8
JournalCirculation research
Volume98
Issue number11
DOIs
Publication statusPublished - Jun 1 2006
Externally publishedYes

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Keywords

  • Ischemia
  • Paracrine effect
  • Preconditioning
  • Remodeling
  • Stem cells

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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