Journal article
MicroRNA-210 enhances cell survival and paracrine potential for cardiac cell therapy while targeting mitophagy
- Abstract:
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The therapeutic potential of presumed cardiac progenitor cells (CPCs) in heart regeneration has garnered significant interest, yet clinical trials have revealed limited efficacy due to challenges in cell survival, retention, and expansion. Priming CPCs to survive the hostile hypoxic environment may be key to enhancing their regenerative capacity. We demonstrate that microRNA-210 (miR-210), known for its role in hypoxic adaptation, significantly improves CPC survival by inhibiting apoptosis through the downregulation of Casp8ap2, a ~40% reduction in caspase activity, and a ~90% decrease in DNA fragmentation. Contrary to the expected induction of Bnip3-dependent mitophagy by hypoxia, miR-210 did not upregulate Bnip3, indicating a distinct anti-apoptotic mechanism. Instead, miR-210 reduced markers of mitophagy and increased mitochondrial biogenesis and oxidative metabolism, suggesting a role in metabolic reprogramming. Furthermore, miR-210 enhanced the secretion of paracrine growth factors from CPCs, with a ~1.6-fold increase in the release of stem cell factor and of insulin growth factor 1, which promoted in vitro endothelial cell proliferation and cardiomyocyte survival. These findings elucidate the multifaceted role of miR-210 in CPC biology and its potential to enhance cell-based therapies for myocardial repair by promoting cell survival, metabolic adaptation, and paracrine signalling.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Version of record, pdf, 9.6MB, Terms of use)
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- Publisher copy:
- 10.3390/jfb16040147
Authors
- Publisher:
- MDPI
- Journal:
- Journal of Functional Biomaterials More from this journal
- Volume:
- 16
- Issue:
- 4
- Article number:
- 147
- Publication date:
- 2025-04-21
- Acceptance date:
- 2025-04-16
- DOI:
- EISSN:
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2079-4983
- Language:
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English
- Keywords:
- Pubs id:
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2119192
- Local pid:
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pubs:2119192
- Deposit date:
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2025-04-21
- ARK identifier:
Terms of use
- Copyright holder:
- Alonaizan et al.
- Copyright date:
- 2025
- Rights statement:
- © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/).
- Licence:
- CC Attribution (CC BY)
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