Endothelial-neurosphere crosstalk in microwell arrays regulates self-renewal and differentiation of human neural stem cells

Kisuk Yang, Jong Seung Lee, Sewoon Han, Yoonhee Jin, Ann Na Cho, Gyeong Eon Chang, Eunji Cheong, Ji Hun Yang, Seok Chung, Seung Woo Cho

Research output: Contribution to journalArticle

Abstract

Control of neural stem cell (NSC) self-renewal and differentiationis of great importance to improve its therapeutic efficacy in the treatment of neurodegenerative diseases. Neurosphere culture for NSC expansion under undifferentiation condition determines the self-renewal capacity and differentiation propensity of NSCs. In this study, we examined the effects of controlled crosstalk between endothelial cells (ECs) and NSC neurospheres on self-renewal, differentiation, and functions of NSCs. Cultures of human fetal NSCs (hfNSCs) or human induced pluripotent stem cell (hiPSC)-derived neural progenitor cells (NPCs) in a microwell array with 500-μm well diameter facilitated cell–cell interaction and self-renewal ability, leading to increased neuronal differentiation and improved electrophysiological functions. Incorporation of ECs into size-controlled hfNSC neurospheres further promoted cell–cell interaction and self-renewal capacity. The decrease in EC density in hfNSC neurospheres effectively promoted cell–cell interaction and self-renewal. Under spontaneous differentiation condition, EC-containing hfNSC neurospheres differentiated into astrocytes rather than neuronal lineages. Therefore, we suggest the engineering of NSCs at neurosphere stage using microwell culture to control neurosphere size and that EC co-culture for vascularization may regulate behaviors, phenotypes, and functions of NSCs, leading to modulation of their therapeutic and regenerative potentials.

Original languageEnglish
JournalJournal of Industrial and Engineering Chemistry
DOIs
Publication statusPublished - 2019 Jan 1

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Keywords

  • Differentiation
  • Endothelial-neurosphere crosstalk
  • Microwell
  • Neural stem cell
  • Neurosphere
  • Self-renewal

ASJC Scopus subject areas

  • Chemical Engineering(all)

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