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Purification and Transplantation of Myogenic Progenitor Cell Derived Exosomes to Improve Cardiac Function in Duchenne Muscular Dystrophic Mice
Published on: April 10, 2019
Current optimized strategies for stem cell-derived extracellular vesicle/exosomes in cardiac repair
Rongrong Wu1, Xinyang Hu2, Jian'an Wang2
1Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, PR China; State Key Laboratory of Transvascular Implantation Devices, Hangzhou 310009, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou 310009, PR China.
Insights
Stem cell-derived extracellular vesicles (EVs), particularly exosomes, show promise for treating ischemic heart disease. Optimizing their production and engineering them for better delivery are key for clinical success.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Biotechnology
Background:
- Ischemic heart diseases are a leading global cause of mortality.
- Stem cell therapy offers potential for cardiac repair, primarily through paracrine factors like extracellular vesicles (EVs).
- Exosomes, a type of EV, are crucial for myocardial repair but face challenges in clinical translation.
Purpose of the Study:
- To review the biogenesis and mechanisms of stem cell-derived EVs/exosomes in cardiac repair.
- To discuss advancements in strategies for high-yield, bioactive EV/exosome production.
- To explore engineering approaches for improved EV/exosome homing and therapeutic potency.
Main Methods:
- Literature review focusing on stem cell-derived EVs/exosomes in cardiac repair.
- Analysis of current optimization strategies for EV/exosome production and engineering.
- Examination of preclinical and clinical translation data for EV/exosome therapy in ischemic heart disease.
Main Results:
- Stem cell-derived EVs/exosomes mediate myocardial repair via paracrine signaling.
- Various strategies are being developed to enhance EV/exosome yield, bioactivity, homing, and retention.
- Preclinical and clinical studies show potential but highlight significant barriers to translation.
Conclusions:
- EV/exosome therapy holds significant promise for treating ischemic heart disease.
- Overcoming challenges in production, bioactivity, and delivery is critical for clinical application.
- Further research and development are needed to facilitate the clinical translation of EV/exosome therapy.
Abstract:
Ischemic heart diseases remain the leading cause of death globally, and stem cell-based therapy has been investigated as a potential approach for cardiac repair. Due to poor survival and engraftment in the cardiac ischemic milieu post transplantation, the predominant therapeutic effects of stem cells act via paracrine actions, by secreting extracellular vesicles (EVs) and/or other factors. Exosomes are nano-sized EVs of endosomal origin, and now viewed as a major contributor in facilitating myocardial repair and regeneration. However, EV/exosome therapy has major obstacles before entering clinical settings, such as limited production yield, unstable biological activity, poor homing efficiency, and low tissue retention. This review aims to provide an overview of the biogenesis and mechanisms of stem cell-derived EV/exosomes in the process of cardiac repair and discuss the current advancements in different optimized strategies to produce high-yield EV/exosomes with higher bioactivity, or engineer them with improved homing efficiency and therapeutic potency. In particular, we outline recent findings toward preclinical and clinical translation of EV/exosome therapy in ischemic heart diseases, and discuss the potential barriers in regard to clinical translation of EV/exosome therapy.
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