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6篇 您的检索式:作者名="Chechneva"
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1Human iPSCs derived astrocytes rescue rotenone-induced mitochondrial dysfunction and dopaminergic neurodegeneration in vitro by donating functional mitochondria显示文摘Background Parkinson’s disease(PD)is one of the neurodegeneration diseases characterized by the gradual loss of dopaminergic(DA)neurons in the substantia nigra region of the brain.Substantial evidence indicates that at the cellular level mitochondrial dysfunction is a key factor leading to pathological features such as neuronal death and accumulation of misfoldedα-synuclein aggregations.Autologous transplantation of healthy purified mitochondria has shown to attenuate phenotypes in vitro and in vivo models of PD.However,there are significant technical difficulties in obtaining large amounts of purified mitochondria with normal function.In addition,the half-life of mitochondria varies between days to a few weeks.Thus,identifying a continuous source of healthy mitochondria via intercellular mitochondrial transfer is an attractive option for therapeutic purposes.In this study,we asked whether iPSCs derived astrocytes can serve as a donor to provide functional mitochondria and rescue injured DA neurons after rotenone exposure in an in vitro model of PD.Methods We generated DA neurons and astrocytes from human iPSCs and hESCs.We established an astroglial-neuronal co-culture system to investigate the intercellular mitochondrial transfer,as well as the neuroprotective effect of mitochondrial transfer.We employed immunocytochemistry and FACS analysis to track mitochondria.Results We showed evidence that iPSCs-derived astrocytes or astrocytic conditioned media(ACM)can rescue DA neurons degeneration via intercellular mitochondrial transfer in a rotenone induced in vitro PD model.Specifically,we showed that iPSCs-derived astrocytes from health spontaneously release functional mitochondria into the media.Mito-Tracker Green tagged astrocytic mitochondria were detected in the ACM and were shown to be internalized by the injured neurons via a phospho-p38 depended pathway.Transferred mitochondria were able to significantly reverse DA neurodegeneration and axonal pruning following exposure to rotenone.When rotenone injured neurons were cultured in presence of ACM depleted of mitochondria(by ultrafiltration),the neuroprotective effects were abolished.Conclusions Our studies provide the proof of principle that iPSCs-derived astrocytes can act as mitochondria donor to the injured DA neurons and attenuate pathology.Using iPSCs derived astrocytes as a donor can provide a novel strategy that can be further developed for cellular therapy for PD.Xiao-Yu Cheng Sangita Biswas Juan Li Cheng-Jie Mao Olga Chechneva Jing Chen Kai Li Jiao Li Jin-Ru Zhang Chun-Feng Liu Wen-Bin Deng 2020Translational Neurodegeneration2020,9,2:7
2A TSPO ligand is protective in a mouse model of multiple sclerosis显示文摘Daniel J. Daugherty Vimal Selvaraj Olga V. Chechneva Xiao‐Bo Liu David E. Pleasure Wenbin Deng 2013EMBO Mol Med2013,,6:1
3Differentiating human stem cells into neurons and glial cells for neural re- pair 显示文摘Selvaraj V Jiang P Chechneva O 2012Front Biosci2012,17,:1
4Differentiating human stem cells into neurons and glial cells for neural repair显示文摘Selvaraj V Jiang P Chechneva O 2012Front Biosci2012,17,:1
5A smoothened receptor agonist is nearoprotective and pro- motes regeneratioa 'after ischemic brain injury 显示文摘CHECHNEVA O V MAYRHOFER F DAUGHERTY D J 2014Cell Death Dis2014,235,:1
6Differentiating human stem cells into neurons and glial cells for neural repair显示文摘Selvaraj V Jiang P Chechneva 0 2012Front Biosci (Landmark Ed)2012,17,:1
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