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Updated: Nov 26, 2025
Purification and Transplantation of Myogenic Progenitor Cell Derived Exosomes to Improve Cardiac Function in Duchenne Muscular Dystrophic Mice
Published on: April 10, 2019
Cardiosphere-derived exosomal microRNAs for myocardial repair in pediatric dilated cardiomyopathy
Kenta Hirai1, Daiki Ousaka2, Yosuke Fukushima1
1Department of Pediatric Cardiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Insights
Cardiosphere-derived cells (CDCs) show promise for treating pediatric dilated cardiomyopathy (DCM). Intracoronary CDC infusion is safe and improves cardiac function in a preclinical model, mediated by exosomes.
Area of Science:
- Regenerative Medicine
- Cardiology
- Cell Therapy
Background:
- Cardiosphere-derived cells (CDCs) show efficacy in single ventricle physiology but their role in pediatric dilated cardiomyopathy (DCM) is unclear.
- Dilated cardiomyopathy (DCM) in children poses significant therapeutic challenges.
Purpose of the Study:
- To evaluate the safety and efficacy of CDCs in a preclinical porcine model of DCM.
- To explore the translational potential of CDCs for pediatric DCM patients.
Main Methods:
- A swine model of DCM was established using intracoronary microsphere injection.
- Preclinical studies involved randomized delivery of CDCs and analysis of CDC-secreted exosomes (CDCex).
- A Phase 1 safety cohort of pediatric DCM patients received CDC infusion.
Main Results:
- Intracoronary CDC administration improved cardiac function and reduced myocardial fibrosis in the porcine DCM model.
- Therapeutic benefits were attributed to CDCex enriched with proangiogenic and cardioprotective microRNAs (miRNAs).
- The Phase 1 safety cohort demonstrated a favorable safety profile and preliminary efficacy over one year.
Conclusions:
- Intracoronary CDC administration is a safe and effective strategy for improving cardiac function in DCM, primarily through CDCex.
- CDCex-derived miRNAs, such as miR-146a-5p, mediate cardioprotection by suppressing inflammation.
- These findings support further clinical trials for pediatric DCM using CDCs and CDCex-derived miRNAs.
Abstract:
Although cardiosphere-derived cells (CDCs) improve cardiac function and outcomes in patients with single ventricle physiology, little is known about their safety and therapeutic benefit in children with dilated cardiomyopathy (DCM). We aimed to determine the safety and efficacy of CDCs in a porcine model of DCM and translate the preclinical results into this patient population. A swine model of DCM using intracoronary injection of microspheres created cardiac dysfunction. Forty pigs were randomized as preclinical validation of the delivery method and CDC doses, and CDC-secreted exosome (CDCex)-mediated cardiac repair was analyzed. A phase 1 safety cohort enrolled five pediatric patients with DCM and reduced ejection fraction to receive CDC infusion. The primary endpoint was to assess safety, and the secondary outcome measure was change in cardiac function. Improved cardiac function and reduced myocardial fibrosis were noted in animals treated with CDCs compared with placebo. These functional benefits were mediated via CDCex that were highly enriched with proangiogenic and cardioprotective microRNAs (miRNAs), whereas isolated CDCex did not recapitulate these reparative effects. One-year follow-up of safety lead-in stage was completed with favorable profile and preliminary efficacy outcomes. Increased CDCex-derived miR-146a-5p expression was associated with the reduction in myocardial fibrosis via suppression of proinflammatory cytokines and transcripts. Collectively, intracoronary CDC administration is safe and improves cardiac function through CDCex in a porcine model of DCM. The safety lead-in results in patients provide a translational framework for further studies of randomized trials and CDCex-derived miRNAs as potential paracrine mediators underlying this therapeutic strategy.
