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 t...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.展开更多
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)+8 种基金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 SciencesCAS Youth Innovation Promotion Association(to Y.W and K.C).
文摘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.
