Insulin concentration is critical in culturing human neural stem cells and neurons

Y. H. Rhee, M. Choi, H. S. Lee, Chang-Hwan Park, S. M. Kim, S. H. Yi, S. M. Oh, H. J. Cha, M. Y. Chang, Sang-Hun Lee

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Cell culture of human-derived neural stem cells (NSCs) is a useful tool that contributes to our understanding of human brain development and allows for the development of therapies for intractable human brain disorders. Human NSC (hNSC) cultures, however, are not commonly used, mainly because of difficulty with consistently maintaining the cells in a healthy state. In this study, we show that hNSC cultures, unlike NSCs of rodent origins, are extremely sensitive to insulin, an indispensable culture supplement, and that the previously reported difficulty in culturing hNSCs is likely because of a lack of understanding of this relationship. Like other neural cell cultures, insulin is required for hNSC growth, as withdrawal of insulin supplementation results in massive cell death and delayed cell growth. However, severe apoptotic cell death was also detected in insulin concentrations optimized to rodent NSC cultures. Thus, healthy hNSC cultures were only produced in a narrow range of relatively low insulin concentrations. Insulin-mediated cell death manifested not only in all human NSCs tested, regardless of origin, but also in differentiated human neurons. The underlying cell death mechanism at high insulin concentrations was similar to insulin resistance, where cells became less responsive to insulin, resulting in a reduction in the activation of the PI3K/Akt pathway critical to cell survival signaling.

Original languageEnglish
Article numbere766
JournalCell Death and Disease
Volume4
Issue number8
DOIs
StatePublished - 2013 Aug 1

Fingerprint

Neural Stem Cells
Insulin
Neurons
Cell Death
Cell Culture Techniques
Rodentia
Critical Pathways
Brain Diseases
Human Development
Growth
Phosphatidylinositol 3-Kinases
Insulin Resistance
Cell Survival
Brain

Keywords

  • Cell apoptosis
  • Human neural stem cells
  • Insulin
  • Insulin resistance
  • PI3K/Akt intracellular signal

Cite this

Rhee, Y. H. ; Choi, M. ; Lee, H. S. ; Park, Chang-Hwan ; Kim, S. M. ; Yi, S. H. ; Oh, S. M. ; Cha, H. J. ; Chang, M. Y. ; Lee, Sang-Hun. / Insulin concentration is critical in culturing human neural stem cells and neurons. In: Cell Death and Disease. 2013 ; Vol. 4, No. 8.
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Insulin concentration is critical in culturing human neural stem cells and neurons. / Rhee, Y. H.; Choi, M.; Lee, H. S.; Park, Chang-Hwan; Kim, S. M.; Yi, S. H.; Oh, S. M.; Cha, H. J.; Chang, M. Y.; Lee, Sang-Hun.

In: Cell Death and Disease, Vol. 4, No. 8, e766, 01.08.2013.

Research output: Contribution to journalArticle

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AU - Choi, M.

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AU - Oh, S. M.

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