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Article: Donation of mitochondria by iPSC-derived mesenchymal stem cells protects retinal ganglion cells against mitochondrial complex I defect-induced degeneration

TitleDonation of mitochondria by iPSC-derived mesenchymal stem cells protects retinal ganglion cells against mitochondrial complex I defect-induced degeneration
Authors
Keywordsmitochondrial defect
induced pluripotent stem cell derived-mesenchymal stem cell
mitochondrial transfer
retinal ganglion cell
Issue Date2019
PublisherIvyspring International Publisher. The Journal's web site is located at http://www.thno.org/
Citation
Theranostics, 2019, v. 9 n. 8, p. 2395-2410 How to Cite?
AbstractRationale: Retinal ganglion cell (RGC) degeneration is extremely hard to repair or regenerate and is often coupled with mitochondrial dysfunction. Mesenchymal stem cells (MSCs)-based treatment has been demonstrated beneficial for RGC against degeneration. However, underlying mechanisms of MSC-provided RGC protection are largely unknown other than neuroprotective paracrine actions. In this study, we sought to investigate whether mitochondrial donation from induced pluripotent stem cell-derived MSC (iPSC-MSCs) could preserve RGC survival and restore retinal function. Methods: iPSC-MSCs were injected into the vitreous cavity of one eye in NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) knockout (KO) and wild type mice. Phosphate buffer saline (PBS) or rotenone treated iPSC-MSCs were injected as control groups. Retinal function was detected by flash electroretinogram (ERG). Whole-mount immunofluorescence (IF), morphometric analysis, confocal microscopy imaging, polymerase chain reaction (PCR) of the retinas were conducted to investigate mitochondrial transfer from human iPSC-MSCs to mouse retina. Quantitative mouse cytokine arrays were carried out to measure retinal inflammatory response under difference treatments. Results: RGC survival in the iPSC-MSC injected retina of Ndufs4 KO mice was significantly increased with improved retinal function. GFP labelled human mitochondria from iPSC-MSC were detected in the RGCs in the retina of Ndufs4 KO mice starting from 96 hours post injection. PCR result showed only human mitochondrial DNA without human nuclear DNA could be detected in the mouse retinas after iPSC-MSC treatment in Ndufs4 KO mice eye. Quantitative cytokine array analysis showed pro-inflammatory cytokines was also downregulated by this iPSC-MSC treatment. Conclusion: Intravitreal transplanted iPSC-MSCs can effectively donate functional mitochondria to RGCs and protect against mitochondrial damage-induced RGC loss.
Persistent Identifierhttp://hdl.handle.net/10722/272731
ISSN
2017 Impact Factor: 8.537
2015 SCImago Journal Rankings: 2.702
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorJiang, D-
dc.contributor.authorXiong, G-
dc.contributor.authorFeng, H-
dc.contributor.authorZhang, Z-
dc.contributor.authorChen, P-
dc.contributor.authorYan, B-
dc.contributor.authorChen, L-
dc.contributor.authorGandhervin, K-
dc.contributor.authorMa, C-
dc.contributor.authorLi, C-
dc.contributor.authorHan, S-
dc.contributor.authorZhang, Y-
dc.contributor.authorLiao, C-
dc.contributor.authorLee, TL-
dc.contributor.authorTse, HF-
dc.contributor.authorFu, QL-
dc.contributor.authorChiu, K-
dc.contributor.authorLian, Q-
dc.date.accessioned2019-08-06T09:15:29Z-
dc.date.available2019-08-06T09:15:29Z-
dc.date.issued2019-
dc.identifier.citationTheranostics, 2019, v. 9 n. 8, p. 2395-2410-
dc.identifier.issn1838-7640-
dc.identifier.urihttp://hdl.handle.net/10722/272731-
dc.description.abstractRationale: Retinal ganglion cell (RGC) degeneration is extremely hard to repair or regenerate and is often coupled with mitochondrial dysfunction. Mesenchymal stem cells (MSCs)-based treatment has been demonstrated beneficial for RGC against degeneration. However, underlying mechanisms of MSC-provided RGC protection are largely unknown other than neuroprotective paracrine actions. In this study, we sought to investigate whether mitochondrial donation from induced pluripotent stem cell-derived MSC (iPSC-MSCs) could preserve RGC survival and restore retinal function. Methods: iPSC-MSCs were injected into the vitreous cavity of one eye in NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) knockout (KO) and wild type mice. Phosphate buffer saline (PBS) or rotenone treated iPSC-MSCs were injected as control groups. Retinal function was detected by flash electroretinogram (ERG). Whole-mount immunofluorescence (IF), morphometric analysis, confocal microscopy imaging, polymerase chain reaction (PCR) of the retinas were conducted to investigate mitochondrial transfer from human iPSC-MSCs to mouse retina. Quantitative mouse cytokine arrays were carried out to measure retinal inflammatory response under difference treatments. Results: RGC survival in the iPSC-MSC injected retina of Ndufs4 KO mice was significantly increased with improved retinal function. GFP labelled human mitochondria from iPSC-MSC were detected in the RGCs in the retina of Ndufs4 KO mice starting from 96 hours post injection. PCR result showed only human mitochondrial DNA without human nuclear DNA could be detected in the mouse retinas after iPSC-MSC treatment in Ndufs4 KO mice eye. Quantitative cytokine array analysis showed pro-inflammatory cytokines was also downregulated by this iPSC-MSC treatment. Conclusion: Intravitreal transplanted iPSC-MSCs can effectively donate functional mitochondria to RGCs and protect against mitochondrial damage-induced RGC loss.-
dc.languageeng-
dc.publisherIvyspring International Publisher. The Journal's web site is located at http://www.thno.org/-
dc.relation.ispartofTheranostics-
dc.rightsTheranostics. Copyright © Ivyspring International Publisher.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectmitochondrial defect-
dc.subjectinduced pluripotent stem cell derived-mesenchymal stem cell-
dc.subjectmitochondrial transfer-
dc.subjectretinal ganglion cell-
dc.titleDonation of mitochondria by iPSC-derived mesenchymal stem cells protects retinal ganglion cells against mitochondrial complex I defect-induced degeneration-
dc.typeArticle-
dc.identifier.emailXiong, G: gyxiong@hku.hk-
dc.identifier.emailYan, B: yanbin14@hku.hk-
dc.identifier.emailZhang, Y: zhangyuelin1999@163.com-
dc.identifier.emailTse, HF: hftse@hkucc.hku.hk-
dc.identifier.emailChiu, K: datwai@hku.hk-
dc.identifier.emailLian, Q: qzlian@hkucc.hku.hk-
dc.identifier.authorityYan, B=rp01940-
dc.identifier.authorityTse, HF=rp00428-
dc.identifier.authorityChiu, K=rp01973-
dc.identifier.authorityLian, Q=rp00267-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.7150/thno.29422-
dc.identifier.pmid31149051-
dc.identifier.pmcidPMC6531297-
dc.identifier.scopuseid_2-s2.0-85066131242-
dc.identifier.hkuros300817-
dc.identifier.hkuros301584-
dc.identifier.volume9-
dc.identifier.issue8-
dc.identifier.spage2395-
dc.identifier.epage2410-
dc.publisher.placeAustralia-

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