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

Autor: Wang R; Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical University, Guangzhou, 510530, China.; Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, 99077, China.; 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.; University of Chinese Academy of Sciences, Beijing, 100049, China., Bao F; Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical University, Guangzhou, 510530, China.; 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., Lu M; Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical University, Guangzhou, 510530, China.; 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., Jia X; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, 510060, China., Xiao J; Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical University, Guangzhou, 510530, China.; 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.; University of Chinese Academy of Sciences, Beijing, 100049, China., Wu Y; Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical University, Guangzhou, 510530, China.; 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., Zhang Q; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, 510060, China. zhangqji@mail.sysu.edu.cn., Liu X; Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical University, Guangzhou, 510530, China. liu_xingguo@gibh.ac.cn.; Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong, 99077, China. liu_xingguo@gibh.ac.cn.; 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. liu_xingguo@gibh.ac.cn.
Jazyk: angličtina
Zdroj: Science China. Life sciences [Sci China Life Sci] 2024 Nov; Vol. 67 (11), pp. 2511-2519. Date of Electronic Publication: 2024 Aug 08.
DOI: 10.1007/s11427-024-2647-8
Abstrakt: 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.
(© 2024. Science China Press.)
Databáze: MEDLINE
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