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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Autores principales: Min Chen, Chunge Ren, Bangqi Ren, Yajie Fang, Qiyou Li, Yuxiao Zeng, Yijian Li, Fang Chen, Baishijiao Bian, Yong Liu
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/740835ed63e349e7bdd93477c85ee13d
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic human retinal progenitor cells
photoreceptor cells
microglia
apoptosis
inflammation
retinal degeneration
Therapeutics. Pharmacology
RM1-950
spellingShingle 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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