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Porous scaffold for mesenchymal cell encapsulation and exosome-based therapy of ischemic diseases
Andreas Czosseck1, Max M Chen1, Helen Nguyen1
1Graduate Institute of Biomedical Materials & Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110, Taiwan.
Insights
A novel encapsulation system improves cell therapy for ischemic diseases by enhancing donor cell survival and secretion of therapeutic extracellular vesicles (EVs), leading to better tissue repair and function.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Cardiovascular Research
Background:
- Ischemic diseases, such as myocardial infarction and limb ischemia, are leading causes of death globally.
- Cell therapy offers potential but faces challenges with poor donor cell survival and retention at the target site.
- Therapeutic benefits of cell therapy are often mediated by paracrine factors, including extracellular vesicles (EVs).
Purpose of the Study:
- To develop and evaluate a porous encapsulation system for enhancing cell therapy efficacy in ischemic diseases.
- To improve donor cell retention, survival, and secretion of therapeutic factors, particularly EVs.
- To assess the therapeutic potential of encapsulated cells in preclinical models of limb ischemia and myocardial infarction.
Main Methods:
- Development of a porous material for encapsulating human cardiac mesenchymal cells.
- In vitro assessment of cell viability, proliferation, and secretion of EVs and growth factors within the scaffold.
- Evaluation of the biological activity of secreted EVs, including hypoxia-protective and pro-angiogenic effects.
- In vivo testing in mouse models of limb ischemia and myocardial infarction to assess therapeutic outcomes and cell retention.
Main Results:
- The encapsulation system supported three-dimensional cell growth and factor secretion.
- Encapsulation increased the secretion of EVs and protective growth factors.
- Secreted EVs demonstrated hypoxia-protective and pro-angiogenic properties in vitro.
- In vivo studies showed improved angiogenesis, blood flow, and preserved cardiac function (ejection fraction) in treated animals.
- The system significantly enhanced donor cell retention and survival compared to direct injection.
Conclusions:
- The developed porous encapsulation system effectively improves cell therapy for ischemic conditions.
- Enhanced cell survival, retention, and EV secretion contribute to improved therapeutic outcomes.
- This technology holds promise for treating ischemic diseases and potentially other conditions requiring cell-based therapies.
Abstract:
Ischemic diseases including myocardial infarction (MI) and limb ischemia are some of the greatest causes of morbidity and mortality worldwide. Cell therapy is a potential treatment but is usually limited by poor survival and retention of donor cells injected at the target site. Since much of the therapeutic effects occur via cell-secreted paracrine factors, including extracellular vesicles (EVs), we developed a porous material for cell encapsulation which would improve donor cell retention and survival, while allowing EV secretion. Human donor cardiac mesenchymal cells were used as a model therapeutic cell and the encapsulation system could sustain three-dimensional cell growth and secretion of therapeutic factors. Secretion of EVs and protective growth factors were increased by encapsulation, and secreted EVs had hypoxia-protective, pro-angiogenic activities in in vitro assays. In a mouse model of limb ischemia the implant improved angiogenesis and blood flow, and in an MI model the system preserved ejection fraction %. In both instances, the encapsulation system greatly extended donor cell retention and survival compared to directly injected cells. This system represents a promising therapy for ischemic diseases and could be adapted for treatment of other diseases in the future.
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