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Updated: Jun 17, 2026
Intramyocardial Cell Delivery: Observations in Murine Hearts
Published on: January 24, 2014
Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a
Xian-Liang Tang1, Gregg Rokosh, Santosh K Sanganalmath
1Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292, USA.
Insights
Cardiac progenitor cells (CPCs) administered via intracoronary infusion improve heart function and structure in old myocardial infarction (MI) scars. This therapy activates endogenous CPCs, offering new hope for chronic heart conditions.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Stem Cell Therapy
Background:
- Acute administration of cardiac progenitor cells (CPCs) improves cardiac function post-myocardial infarction (MI).
- Current clinical limitations prevent timely CPC administration after acute MI due to expansion time.
- The therapeutic potential of CPCs in established myocardial infarction (scar tissue) remains largely unexplored.
Purpose of the Study:
- To investigate the efficacy of CPCs in a clinically relevant model of old myocardial infarction (MI).
- To determine if intracoronary CPC infusion benefits structural and functional aspects of chronic ischemic heart disease.
Main Methods:
- Rats with established MI underwent intracoronary infusion of CPCs or vehicle.
- Cardiac function, myocardial viability, and fibrosis were assessed 35 days post-infusion.
- Cellular differentiation and proliferation of both transplanted and endogenous CPCs were analyzed.
Main Results:
- CPC treatment significantly improved left ventricular function and increased viable myocardium in the scar region.
- Reduced fibrosis in non-infarcted areas was observed in CPC-treated rats.
- Transplanted CPCs showed limited differentiation, but increased proliferation and cardiac protein expression of endogenous CPCs were evident.
Conclusions:
- Intracoronary CPC administration yields significant structural and functional benefits in chronic MI.
- The therapeutic effects are likely mediated by paracrine signaling, including the activation of endogenous CPCs.
- This study provides the first evidence of CPC efficacy in old MI and demonstrates their ability to activate endogenous CPCs, paving the way for autologous cell therapies.
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.
