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

Yizhao Ma, Kaizhe Wang, Jiabin Pan, Zhaohuan Fan, Changhai Tian, Xiaobei Deng, Kangmu Ma, Xiaohuan Xia, Yunlong Huang, Jialin C Zheng

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 ERK 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.

Original languageEnglish (US)
Pages (from-to)322-334
Number of pages13
JournalNeurobiology of Disease
Volume124
DOIs
StatePublished - Apr 1 2019

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Neural Stem Cells
Phosphotransferases
Stem Cells
Extracellular Signal-Regulated MAP Kinases
Therapeutic Uses
Intercellular Signaling Peptides and Proteins
Extracellular Vesicles
Nervous System Diseases
Astrocytes
Proteomics
Transcription Factors
Fibroblasts
Cell Count
Cell Proliferation
Brain
Therapeutics

Keywords

  • Cellular reprogramming
  • ERK pathways
  • Extracellular vesicles
  • Growth factors
  • Neural progenitor cells
  • Proliferation

ASJC Scopus subject areas

  • Neurology

Cite this

Induced neural progenitor cells abundantly secrete extracellular vesicles and promote the proliferation of neural progenitors via extracellular signal–regulated kinase pathways. / Ma, Yizhao; Wang, Kaizhe; Pan, Jiabin; Fan, Zhaohuan; Tian, Changhai; Deng, Xiaobei; Ma, Kangmu; Xia, Xiaohuan; Huang, Yunlong; Zheng, Jialin C.

In: Neurobiology of Disease, Vol. 124, 01.04.2019, p. 322-334.

Research output: Contribution to journalArticle

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