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Updated: Dec 14, 2025
Delayed Intramyocardial Delivery of Stem Cells after Ischemia Reperfusion Injury in a Murine Model
Published on: September 3, 2020
Intracoronary Administration of Allogeneic Cardiosphere-Derived Cells Immediately Prior to Reperfusion in Pigs With
Vasileios Sousonis1,2, Titika Sfakianaki1, Argirios Ntalianis1
1Third Department of Cardiology, University of Athens School of Medicine, Athens, Greece.
Insights
Administering allogeneic cardiosphere-derived cells (CDCs) before reperfusion improves cell delivery and enhances cardiac repair in acute myocardial infarction (AMI) models. This timing strategy offers long-term benefits for heart function and reduces adverse remodeling.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Cell Therapy
Background:
- Allogeneic cardiosphere-derived cells (CDCs) show cardioprotective effects in acute myocardial infarction (AMI) animal models.
- The no-reflow phenomenon impedes cell therapy efficacy by limiting delivery to microvascular obstruction areas post-reperfusion.
- Early cell administration may improve delivery and therapeutic outcomes in AMI.
Purpose of the Study:
- To investigate if administering CDCs before reperfusion enhances cardioprotection in AMI.
- To determine the optimal safe dosage and timing for intracoronary CDC infusion.
- To evaluate the long-term efficacy of pre-reperfusion CDC therapy on cardiac function and remodeling.
Main Methods:
- Dose-optimization and safety studies were conducted in a porcine AMI model.
- Cell retention was quantified using polymerase chain reaction after pre- and post-reperfusion delivery.
- A randomized, placebo-controlled trial assessed long-term outcomes of pre-reperfusion CDC infusion.
Main Results:
- Maximum safe doses of 5 and 10 million CDCs were identified for pre- and post-reperfusion administration, respectively.
- Pre-reperfusion CDC delivery resulted in significantly higher cardiac cell retention.
- CDC therapy at 30 days post-MI reduced scar size, improved systolic function, and attenuated adverse remodeling.
Conclusions:
- Intracoronary infusion of allogeneic CDCs prior to reperfusion is feasible and safe in a porcine AMI model.
- Pre-reperfusion CDC administration enhances cell delivery and provides long-term cardioprotective benefits.
- This timing strategy improves cardiac function and reduces pathological remodeling post-myocardial infarction.
Background:
Allogeneic cardiosphere-derived cells (CDCs) exert cardioprotective effects when administered intracoronarily after reperfusion in animal models of acute myocardial infarction (AMI). The "no-reflow" phenomenon develops rapidly post-reperfusion and may undermine the efficacy of cell therapy, due to poor cell delivery in areas of microvascular obstruction (MVO). We hypothesized that CDC-induced cardioprotection would be enhanced by cell administration prior to reperfusion, when microvasculature is still relatively intact, to facilitate widespread cell delivery within the ischemic area.
Methods And Results:
We studied 81 farm pigs; 55 completed the specified protocols. A dose-optimization study in infarcted pigs demonstrated that the doses of 5 million and 10 million CDCs are the maximum safe doses that can be administered intracoronarily at 5 minutes prior to and at 5 minutes post-reperfusion, respectively, without aggravating MVO. Quantification of acute cell retention by polymerase chain reaction demonstrated that cell delivery prior to reperfusion resulted in higher cardiac cell retention compared to delivery post-reperfusion. We then performed a randomized, placebo-controlled study to assess the long-term efficacy of intracoronary infusion of 5 million allogeneic CDCs, delivered at 5 minutes prior to reperfusion, in a porcine model of AMI. The CDC therapy resulted in decreased scar size, improved regional systolic function, and attenuation of adverse cardiac remodeling (manifested as preserved global systolic function, preserved end-systolic volume, and decreased interstitial fibrosis) compared to placebo at 30 days post-MI.
Conclusions:
Dose-optimized intracoronary infusion of allogeneic CDCs prior to reperfusion in a porcine model of AMI is feasible, safe and confers long-term benefits.
