Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury  

作　　者：Tong Li Hui-Min Xing Hai-Dong Qian Qiao Gao Sheng-Lan Xu Hua Ma Zai-Long Chi 

机构地区：[1]State Key Laboratory of Ophthalmology,Optometry and Visual Science,Eye Hospital,Wenzhou Medical University,Wenzhou,Zhejiang Province,China [2]National Clinical Research Center for Ocular Diseases,Eye Hospital,Wenzhou Medical University,Wenzhou,Zhejiang Province,China

出　　处：《Neural Regeneration Research》2025年第2期587-597,共11页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.82271114;the Natural Science Foundation of Zhejiang Province of China,No.LZ22H120001(both to ZLC).

摘　　要：Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

关 键 词：EXOSOME miRNA neural progenitor cell NEURODEGENERATION NEUROINFLAMMATION neuroprotection optic nerve crush optic neuropathy retinal ganglion cell small extracellular vesicles 

分 类 号：R774.6[医药卫生—眼科] R-332[医药卫生—临床医学]