SDF-1 expression by mesenchymal stem cells results in trophic support of cardiac myocytes after myocardial infarction

Ming Zhang, Niladri Mal, Matthew Kiedrowski, Matthews Chacko, Arman T. Askari, Zoran B. Popovic, Omer N. Koc, Marc S. Penn

Research output: Contribution to journalArticle

Abstract

Stem cell transplantation at the time of acute myocardial infarction (AMI) improves cardiac function. Whether the improved cardiac function results from regeneration of cardiac myocytes, modulation of remodeling, or preservation of injured tissue through paracrine mechanisms is actively debated. Because no specific stem cell population has been shown to be optimal, we investigated whether the benefit of stem cell transplantation could be attributed to a trophic effect on injured myocardium. Mesenchymal stem cells secrete SDF-1 and the interaction of SDF-1 with its receptor, CXCR4, increases survival of progenitor cells. Therefore, we compared the effects of MSC and MSC engineered to overexpress SDF-1 on cardiac function after AMI. Tail vein infusion of syngeneic MSC and MSC:SDF-1 1 day after AMI in the Lewis rat led to improved cardiac function by echocardiography by 70.7% and 238.8%, respectively, compared with saline controls 5 wk later. The beneficial effects of MSC and MSC:SDF-1 transplantation were mediated primarily through preservation, not regeneration of cardiac myocytes within the infarct zone. The direct effect of SDF-1 on cardiac myocytes was due to the observation that, between 24 and 48 h after AMI, SDF-1-expressing MSC increased cardiac myocyte survival, vascular density (18.2±4.0 vs. 7.6±2.3 vessels/mm2, P

Original languageEnglish (US)
Pages (from-to)3197-3207
Number of pages11
JournalFASEB Journal
Volume21
Issue number12
DOIs
StatePublished - Oct 2007
Externally publishedYes

    Fingerprint

Keywords

  • Cardiac regeneration
  • HSC
  • SDF-1-based therapy
  • Transplantation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology
  • Medicine(all)

Cite this

Zhang, M., Mal, N., Kiedrowski, M., Chacko, M., Askari, A. T., Popovic, Z. B., Koc, O. N., & Penn, M. S. (2007). SDF-1 expression by mesenchymal stem cells results in trophic support of cardiac myocytes after myocardial infarction. FASEB Journal, 21(12), 3197-3207. https://doi.org/10.1096/fj.06-6558com