Human Retinal Progenitor Cells Derived Small Extracellular Vesicles Delay Retinal Degeneration: A Paradigm for Cell-free Therapy
Retinal degeneration is a leading cause of irreversible vision impairment and blindness worldwide. Previous studies indicate that subretinal injection of human retinal progenitor cells (hRPCs) can delay the progression of retinal degeneration, preserve retinal function, and protect photoreceptor cel...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:740835ed63e349e7bdd93477c85ee13d2021-12-01T14:02:50ZHuman Retinal Progenitor Cells Derived Small Extracellular Vesicles Delay Retinal Degeneration: A Paradigm for Cell-free Therapy1663-981210.3389/fphar.2021.748956https://doaj.org/article/740835ed63e349e7bdd93477c85ee13d2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.748956/fullhttps://doaj.org/toc/1663-9812Retinal degeneration is a leading cause of irreversible vision impairment and blindness worldwide. Previous studies indicate that subretinal injection of human retinal progenitor cells (hRPCs) can delay the progression of retinal degeneration, preserve retinal function, and protect photoreceptor cells from death, albeit the mechanism is not well understood. In this study, small extracellular vesicles derived from hRPCs (hRPC-sEVs) were injected into the subretinal space of retinal dystrophic RCS rats. We find that hRPC-sEVs significantly preserve the function of retina and thickness of the outer nuclear layer (ONL), reduce the apoptosis of photoreceptors in the ONL, and suppress the inflammatory response in the retina of RCS rats. In vitro, we have shown that hRPC-sEV treatment could significantly reserve the low-glucose preconditioned apoptosis of photoreceptors and reduce the expression of pro-inflammatory cytokines in microglia. Pathway analysis predicted the target genes of hRPC-sEV microRNAs involved in inflammation related biological processes and significantly enriched in processes autophagy, signal release, regulation of neuron death, and cell cycle. Collectively, our study suggests that hRPC-sEVs might be a favorable agent to delay retinal degeneration and highlights as a new paradigm for cell-free therapy.Min ChenMin ChenChunge RenChunge RenBangqi RenBangqi RenYajie FangYajie FangQiyou LiQiyou LiYuxiao ZengYuxiao ZengYijian LiYijian LiFang ChenBaishijiao BianBaishijiao BianBaishijiao BianYong LiuYong LiuFrontiers Media S.A.articlehuman retinal progenitor cellsphotoreceptor cellsmicrogliaapoptosisinflammationretinal degenerationTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
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human retinal progenitor cells photoreceptor cells microglia apoptosis inflammation retinal degeneration Therapeutics. Pharmacology RM1-950 |
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human retinal progenitor cells photoreceptor cells microglia apoptosis inflammation retinal degeneration Therapeutics. Pharmacology RM1-950 Min Chen Min Chen Chunge Ren Chunge Ren Bangqi Ren Bangqi Ren Yajie Fang Yajie Fang Qiyou Li Qiyou Li Yuxiao Zeng Yuxiao Zeng Yijian Li Yijian Li Fang Chen Baishijiao Bian Baishijiao Bian Baishijiao Bian Yong Liu Yong Liu Human Retinal Progenitor Cells Derived Small Extracellular Vesicles Delay Retinal Degeneration: A Paradigm for Cell-free Therapy |
description |
Retinal degeneration is a leading cause of irreversible vision impairment and blindness worldwide. Previous studies indicate that subretinal injection of human retinal progenitor cells (hRPCs) can delay the progression of retinal degeneration, preserve retinal function, and protect photoreceptor cells from death, albeit the mechanism is not well understood. In this study, small extracellular vesicles derived from hRPCs (hRPC-sEVs) were injected into the subretinal space of retinal dystrophic RCS rats. We find that hRPC-sEVs significantly preserve the function of retina and thickness of the outer nuclear layer (ONL), reduce the apoptosis of photoreceptors in the ONL, and suppress the inflammatory response in the retina of RCS rats. In vitro, we have shown that hRPC-sEV treatment could significantly reserve the low-glucose preconditioned apoptosis of photoreceptors and reduce the expression of pro-inflammatory cytokines in microglia. Pathway analysis predicted the target genes of hRPC-sEV microRNAs involved in inflammation related biological processes and significantly enriched in processes autophagy, signal release, regulation of neuron death, and cell cycle. Collectively, our study suggests that hRPC-sEVs might be a favorable agent to delay retinal degeneration and highlights as a new paradigm for cell-free therapy. |
format |
article |
author |
Min Chen Min Chen Chunge Ren Chunge Ren Bangqi Ren Bangqi Ren Yajie Fang Yajie Fang Qiyou Li Qiyou Li Yuxiao Zeng Yuxiao Zeng Yijian Li Yijian Li Fang Chen Baishijiao Bian Baishijiao Bian Baishijiao Bian Yong Liu Yong Liu |
author_facet |
Min Chen Min Chen Chunge Ren Chunge Ren Bangqi Ren Bangqi Ren Yajie Fang Yajie Fang Qiyou Li Qiyou Li Yuxiao Zeng Yuxiao Zeng Yijian Li Yijian Li Fang Chen Baishijiao Bian Baishijiao Bian Baishijiao Bian Yong Liu Yong Liu |
author_sort |
Min Chen |
title |
Human Retinal Progenitor Cells Derived Small Extracellular Vesicles Delay Retinal Degeneration: A Paradigm for Cell-free Therapy |
title_short |
Human Retinal Progenitor Cells Derived Small Extracellular Vesicles Delay Retinal Degeneration: A Paradigm for Cell-free Therapy |
title_full |
Human Retinal Progenitor Cells Derived Small Extracellular Vesicles Delay Retinal Degeneration: A Paradigm for Cell-free Therapy |
title_fullStr |
Human Retinal Progenitor Cells Derived Small Extracellular Vesicles Delay Retinal Degeneration: A Paradigm for Cell-free Therapy |
title_full_unstemmed |
Human Retinal Progenitor Cells Derived Small Extracellular Vesicles Delay Retinal Degeneration: A Paradigm for Cell-free Therapy |
title_sort |
human retinal progenitor cells derived small extracellular vesicles delay retinal degeneration: a paradigm for cell-free therapy |
publisher |
Frontiers Media S.A. |
publishDate |
2021 |
url |
https://doaj.org/article/740835ed63e349e7bdd93477c85ee13d |
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