MSC-mediated mitochondrial transfer restores mitochondrial DNA and function in neural progenitor cells of Leber’s hereditary optic neuropathy  

作　　者：Rui Wang Feixiang Bao Manjiao Lu Xiaoyun Jia Jiahui Xiao Yi Wu Qingjiong Zhang Xingguo Liu 

机构地区：[1]Joint School of Life Sciences,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences/Guangzhou Medical University,Guangzhou 510530,China [2]Centre for Regenerative Medicine and Health,Hong Kong Institute of Science&Innovation,Chinese Academy of Sciences,Hong Kong 99077,China [3]Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine,Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine,China-New Zealand Joint Laboratory on Biomedicine and Health,CUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative Medicine,GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre,Institute for Stem Cell and Regeneration,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,China [4]State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center,Sun Yat-sen University,Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science,Guangzhou 510060,China [5]University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Science China(Life Sciences)》2024年第11期2511-2519,共9页中国科学（生命科学英文版）

基　　金：financially supported by the National Key Research and Development Program of China(2022YFE0210100,2023YFE0210100,2022YFA1103800,2019YFA0904500);the National Natural Science Foundation projects of China(32025010,92157202,32241002,92254301,92357302,32261160376,31970709,32070729,32100619,32170747,32322022,32370782,32371007,32300608,32300620);NSFC/RGC Joint Grant Scheme 2022/2023(N_CUHK 428/22);the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0480000);the Key Research Program,CAS(ZDBS-ZRKJZ-TLC003);International Cooperation Program,CAS(154144KYSB20200006);CAS Project for Young Scientists in Basic Research(YSBR-075);Guangdong Province Science and Technology Program(2023B0303000023,2023B1111050005,2023A1515030231,2022A1515110493,2023B1212060050,2021A1515012513,2021B1515020096,2022A1515012616,2022A1515110951,2023B1212120009,2024A1515010782,2024B1515040020,2024A1515030120);Guangzhou Science and Technology Program(202102021037,202102020827,202102080066,202206060002,2023A04J0414);Health@InnoHK funding support from the Innovation Technology Commission of the Hong Kong SAR,Basic Research Project of Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences;CAS Youth Innovation Promotion Association(to Y.W and K.C).

摘　　要：Leber’s hereditary optic neuropathy(LHON)is a debilitating mitochondrial disease associated with mutations in mitochondrial DNA(mtDNA).Unfortunately,the available treatment options for LHON patients are limited due to challenges in mitochondrial replacement.In our study,we reprogramming LHON urine cells into induced pluripotent stem cells(iPSCs)and differentiating them into neural progenitor cells(NPCs)and neurons for disease modeling.Our research revealed that LHON neurons exhibited significantly higher levels of mtDNA mutations and reduced mitochondrial function,confirming the disease phenotype.However,through co-culturing LHON iPSC-derived NPCs with mesenchymal stem cells(MSCs),we observed a remarkable rescue of mutant mtDNA and a significant improvement in mitochondrial metabolic function in LHON neurons.These findings suggest that co-culturing with MSCs can enhance mitochondrial function in LHON NPCs,even after their differentiation into neurons.This discovery holds promise as a potential therapeutic strategy for LHON patients.

关 键 词：MITOCHONDRIA mitochondrial DNA mitochondrial diseases induced pluripotent stem cells stem cells METABOLISM energy mesenchymal stem cells 

分 类 号：R774.6[医药卫生—眼科]