Extracellular vesicles from organoid-derived human retinal progenitor cells prevent lipid overload-induced retinal pigment epithelium injury by regulating fatty acid metabolism

作者全名："Gao, Hui; Zeng, Yuxiao; Huang, Xiaona; Luodan, A.; Liang, Qingle; Xie, Jing; Lin, Xi; Gong, Jing; Fan, Xiaotang; Zou, Ting; Xu, Haiwei"

作者地址："[Gao, Hui; Zeng, Yuxiao; Huang, Xiaona; Luodan, A.; Xie, Jing; Lin, Xi; Gong, Jing; Zou, Ting; Xu, Haiwei] Army Med Univ, Third Mil Med Univ, Southwest Eye Hosp, Southwest Hosp, Chongqing, Peoples R China; [Gao, Hui; Zeng, Yuxiao; Huang, Xiaona; Luodan, A.; Xie, Jing; Lin, Xi; Gong, Jing; Zou, Ting; Xu, Haiwei] Key Lab Visual Damage & Regenerat Restorat Chongq, Chongqing, Peoples R China; [Liang, Qingle] Army Med Univ, Third Mil Med Univ, Affiliated Hosp 1, Dept Clin Lab Med, Chongqing, Peoples R China; [Gong, Jing] Chongqing Univ, Coll Bioengn, Key Lab Biorheol Sci & Technol, Minist Educ, Chongqing, Peoples R China; [Fan, Xiaotang] Army Med Univ, Third Mil Med Univ, Sch Psychol, Dept Mil Cognit Psychol, Chongqing, Peoples R China; [Zou, Ting] Chongqing Med Univ, Dept Ophthalmol, Affiliated Hosp 2, Chongqing, Peoples R China"

通信作者："Zou, T; Xu, HW (通讯作者)，Army Med Univ, Third Mil Med Univ, Southwest Eye Hosp, Southwest Hosp, Chongqing, Peoples R China.; Zou, T; Xu, HW (通讯作者)，Key Lab Visual Damage & Regenerat Restorat Chongq, Chongqing, Peoples R China.; Fan, XT (通讯作者)，Army Med Univ, Third Mil Med Univ, Sch Psychol, Dept Mil Cognit Psychol, Chongqing, Peoples R China.; Zou, T (通讯作者)，Chongqing Med Univ, Dept Ophthalmol, Affiliated Hosp 2, Chongqing, Peoples R China."

来源：JOURNAL OF EXTRACELLULAR VESICLES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001131567300001

JCR分区：Q1

影响因子：16

年份：2024

卷号：13

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：extracellular vesicles; lipid metabolism; retinal organoids; retinal pigment epithelium cells; retinal progenitor cells

摘要："Retinal degeneration (RD), a group of diseases leading to irreversible vision loss, is characterised by retinal pigment epithelium (RPE) or retinal neuron damage and loss. With fewer risks of immune rejection and tumorigenesis, stem cell-secreted extracellular vesicles (EVs) offer a new cell-free therapeutic paradigm for RD, which remains to be investigated. Human retinal organoid-derived retinal progenitor cells (hERO-RPCs) are an easily accessible and advanced cell source for RD treatment. However, hERO-RPCs-derived EVs require further characterisation. Here, we compared the characteristics of EVs from hERO-RPCs (hRPC-EVs) with those of human embryonic stem cell (hESC)-derived EVs (hESC-EVs) as controls. Based on in-depth proteomic analysis, we revealed remarkable differences between hRPC-EVs and hESC-EVs. A comparison between EVs and their respective cells of origin demonstrated that the protein loading of hRPC-EVs was more selective than that of hESC-EVs. In particular, hESC-EVs were enriched with proteins related to angiogenesis and cell cycle, whereas hRPC-EVs were enriched with proteins associated with immune modulation and retinal development. More importantly, compared with that of hESC-EVs, hRPC-EVs exhibited a lower correlation with cell proliferation and a unique capacity to regulate lipid metabolism. It was further confirmed that hRPC-EVs potentially eliminated lipid deposits, inhibited lipotoxicity and oxidative stress, and enhanced phagocytosis and survival of oleic acid-treated ARPE-19 cells. Mechanistically, hRPC-EVs are integrated into the mitochondrial network of oleic acid-treated ARPE-19 cells, and increased the level of mitochondrial fatty acid beta-oxidation-related proteins. Thus, organoid-derived hRPC-EVs represent a promising source of cell-free therapy for RD, especially for blinding diseases related to abnormal lipid metabolism in RPE cells."

基金机构："National Natural Science Foundation of China; National Key Research and Development Program of China [2021YFA1101203, 2018YFA0107302]; [31930068]; [82000945]"

基金资助正文："We would like to thanks Dr. Jie Hao in State Key Laboratory of Stem Cells and Reproductive Biology, Institude of Zoology, Chinese Academy of Sciences for providing the hESC cell line Q-CTS-hESC-2. This study was supported by funding from the National Natural Science Foundation of China (No. 31930068, 82000945), the National Key Research and Development Program of China (NO. 2021YFA1101203, 2018YFA0107302)."