Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction

Xian Liang Tang, Gregg Rokosh, Santosh K. Sanganalmath, Fangping Yuan, Hiroshi Sato, Jianyao Mu, Shujing Dai, Chengxin Li, Ning Chen, Yong Peng, Buddhadeb Dawn, Greg Hunt, Annarosa Leri, Jan Kajstura, Sumit Tiwari, Gregg Shirk, Piero Anversa, Roberto Bolli

Research output: Contribution to journalArticle

Abstract

Background: Administration of cardiac progenitor cells (CPCs) 4 hours after reperfusion ameliorates left ventricular function in rats with acute myocardial infarction (MI). Clinically, however, this approach is not feasible, because expansion of autologous CPCs after acute MI requires several weeks. Therefore, we sought to determine whether CPCs are beneficial in the more clinically relevant setting of an old MI (scar). Methods and Results: One month after coronary occlusion/reperfusion, rats received an intracoronary infusion of vehicle or enhanced green fluorescent protein-labeled CPCs. Thirty-five days later, CPC-treated rats exhibited more viable myocardium in the risk region, less fibrosis in the noninfarcted region, and improved left ventricular function. Cells that stained positive for enhanced green fluorescent protein that expressed cardiomyocyte, endothelial, and vascular smooth muscle cell markers were observed only in 7 of 17 treated rats and occupied only 2.6% and 1.1% of the risk and noninfarcted regions, respectively. Transplantation of CPCs was associated with increased proliferation and expression of cardiac proteins by endogenous CPCs. Conclusions: Intracoronary administration of CPCs in the setting of an old MI produces beneficial structural and functional effects. Although exogenous CPCs can differentiate into new cardiac cells, this mechanism is not sufficient to explain the benefits, which suggests paracrine effects; among these, the present data identify activation of endogenous CPCs. This is the first report that CPCs are beneficial in the setting of an old MI when given by intracoronary infusion, the most widely applicable therapeutic approach in patients. Furthermore, this is the first evidence that exogenous CPC administration activates endogenous CPCs. These results open the door to new therapeutic applications for the use of autologous CPCs in patients with old MI and chronic ischemic cardiomyopathy.

Original languageEnglish (US)
Pages (from-to)293-305
Number of pages13
JournalCirculation
Volume121
Issue number2
DOIs
StatePublished - Jan 1 2010

Keywords

  • Myocardial infarction
  • Progenitor cells
  • Regeneration
  • Reperfusion
  • Stem cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Tang, X. L., Rokosh, G., Sanganalmath, S. K., Yuan, F., Sato, H., Mu, J., Dai, S., Li, C., Chen, N., Peng, Y., Dawn, B., Hunt, G., Leri, A., Kajstura, J., Tiwari, S., Shirk, G., Anversa, P., & Bolli, R. (2010). Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction. Circulation, 121(2), 293-305. https://doi.org/10.1161/CIRCULATIONAHA.109.871905