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 

作者机构：Joint School of Life SciencesGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou Medical University Centre for Regenerative Medicine and HealthHong Kong Institute of Science&InnovationChinese Academy of Sciences Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineCUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative MedicineGIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research CentreInstitute for Stem Cell and RegenerationGuangzhou Institutes of Biomedicine and HealthChinese Academy of Sciences University of Chinese Academy of Sciences State Key Laboratory of OphthalmologyZhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual Science 

出 版 物：《Science China Life Sciences》 (中国科学:生命科学(英文版))

年 卷 期：2024年

核心收录：

学科分类：1002[医学-临床医学] 100212[医学-眼科学] 10[医学] 

基　　金：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) 

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 *** 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 *** research revealed that LHON neurons exhibited significantly higher levels of mtDNA mutations and reduced mitochondrial function,confirming the disease ***,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 *** findings suggest that co-culturing with MSCs can enhance mitochondrial function in LHON NPCs,even after their differentiation into *** discovery holds promise as a potential therapeutic strategy for LHON patients.