Induced neural progenitor cells abundantly secrete extracellular vesicles and promote the proliferation of neural progenitors via extracellular signal-regulated kinase pathways

NEUROBIOLOGY OF DISEASE

卷:124

Article

Ma, Yizhao¹  Wang, Kaizhe¹  Pan, Jiabin¹  Fan, Zhaohuan¹  Tian, Changhai^1,3,4  Deng, Xiaobei¹  Ma, Kangmu^1,3,4  Xia, Xiaohuan¹  Huang, Yunlong^1,3,4  Zheng, Jialin C.^1,2,3,4,5 

[1] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Ctr Translat Neurodegenerat & Regenerat Therapy, Shanghai 200072, Peoples R China

[2] Tongji Univ, Collaborat Innovat Ctr Brain Sci, Shanghai 200092, Peoples R China

[3] Univ Nebraska Med Ctr, Dept Pharmacol, Omaha, NE 68198 USA

[4] Univ Nebraska Med Ctr, Dept Expt Neurosci, Omaha, NE 68198 USA

[5] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA

关键词: Cellular reprogramming;    Neural progenitor cells;    Extracellular vesicles;    Proliferation;    Growth factors;    ERK pathways;   

DOI  :  10.1016/j.nbd.2018.12.003

来源: Elsevier

【 摘 要 】

Neural stem/progenitor cells (NPCs) are known to have potent therapeutic effects in neurological disorders through the secretion of extracellular vesicles (EVs). Despite the therapeutic potentials, the numbers of NPCs are limited in the brain, curbing the further use of EVs in the disease treatment. To overcome the limitation of NPC numbers, we used a three transcription factor (Brn2, Sox2, and Foxg1) somatic reprogramming approach to generate induced NPCs (iNPCs) from mouse fibroblasts and astrocytes. The resulting iNPCs released significantly higher numbers of EVs compared with wild-type NPCs (WT-NPCs). Furthermore, iNPCs-derived EVs (iNPC-EVs) promoted NPC function by increasing the proliferative potentials of WT-NPCs. Characterizations of EV contents through proteomics analysis revealed that iNPC-EVs contained higher levels of growth factor-associated proteins that were predicted to activate the down-stream extracellular signal-regulated kinase (ERK) pathways. As expected, the proliferative effects of iNPC-derived EVs on WT-NPCs can be blocked by an MU( pathway inhibitor. Our data suggest potent therapeutic effects of iNPC-derived EVs through the promotion of NPC proliferation, release of growth factors, and activation of ERK pathways. These studies will help develop highly efficient cell free therapeutic strategies for the treatment of neurological diseases.

【 授权许可】

Free