Efficient and rapid derivation of primitive neural stem cells and generation of brain subtype neurons from human pluripotent stem cells

Yiping Yan, Soojung Shin, Shekhar Jha Balendu, Qiuyue Liu, Jianting Sheng, Fuhai Li, Ming Zhan, Janine Davis, Kapil Bharti, Xianmin Zeng, Mahendra Rao, Nasir Malik, Mohan C. Vemuri

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

Human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, are unique cell sources for disease modeling, drug discovery screens, and cell therapy applications. The first step in producing neural lineages from hPSCs is the generation of neural stem cells (NSCs). Current methods of NSC derivation involve the time-consuming, laborintensive steps of an embryoid body generation or coculture with stromal cell lines that result in low-efficiency derivation of NSCs. In this study, we report a highly efficient serum-free pluripotent stem cell neural induction medium that can induce hPSCs into primitive NSCs (pNSCs) in 7 days, obviating the need for time-consuming, laborious embryoid body generation or rosette picking. The pNSCs expressed the neural stem cell markers Pax6, Sox1, Sox2, and Nestin; were negative for Oct4; could be expanded for multiple passages; and could be differentiated into neurons, astrocytes, and oligodendrocytes, in addition to the brain region-specific neuronal subtypes GABAergic, dopaminergic, and motor neurons. Global gene expression of the transcripts of pNSCs was comparable to that of rosette-derived and human fetal-derived NSCs. This work demonstrates an efficient method to generate expandable pNSCs, which can be further differentiated into central nervous system neurons and glia with temporal, spatial, and positional cues of brain regional heterogeneity. This method of pNSC derivation sets the stage for the scalable production of clinically relevant neural cells for cell therapy applications in good manufacturing practice conditions.

Original languageEnglish (US)
Pages (from-to)862-870
Number of pages9
JournalStem Cells Translational Medicine
Volume2
Issue number11
DOIs
StatePublished - 2013

Keywords

  • Astrocytes
  • Cell culture
  • Nestin
  • Neural differentiation
  • Neural induction
  • Neural stem cell
  • Neuron
  • Oligodendrocytes

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology

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