Effect of neurosphere size on the growth rate of human neural stem/progenitor cells

Hideki Mori, Kazuaki Ninomiya, Masahiro Kino-Oka, Tomoko Shofuda, Mohammed Omedul Islam, Mami Yamasaki, Hideyuki Okano, Masahito Taya, Yonehiro Kanemura

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Neural stem/progenitor cells (NSPCs) proliferate as aggregates in vitro, but the mechanism of aggregation is not fully understood. Here, we report that aggregation promotes the proliferation of NSPCs. We found that the proliferation rate was linear and depended on the size of the aggregate; that is, the population doubling time of the NSPCs gradually decreased as the diameter approached 250 μm and flattened to a nearly constant value beyond this diameter. Given this finding, and with the intent of enhancing the efficiency of human NSPC expansion, we induced the NSPCs to form aggregates close to 250 μm in diameter quickly by culturing them in plates with U-bottomed wells. The NSPCs formed aggregates effectively in the U-bottomed wells, with cell numbers approximately 1.5 times greater than those in the aggregates that formed spontaneously in flat-bottomed wells. In addition, this effect of aggregation involved cell-cell signaling molecules of the Notch1 pathway. In the U-bottomed wells, Hes1 and Hes5, which are target genes of the Notch signal, were expressed at higher levels than in the control, flat-bottomed wells. The amount of cleaved Notch1 was also higher in the cells cultured in the U-bottomed wells. The addition of γ-secretase inhibitor, which blocks Notch signaling, suppressed cell proliferation in the U-bottomed wells. These results suggest that the three-dimensional architecture of NSPC aggregates would create a microenvironment that promotes the proliferation of human NSPCs.

Original languageEnglish
Pages (from-to)1682-1691
Number of pages10
JournalJournal of Neuroscience Research
Volume84
Issue number8
DOIs
Publication statusPublished - 2006 Dec

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Neural Stem Cells
Stem Cells
Growth
Amyloid Precursor Protein Secretases
Cell Aggregation
Cultured Cells
Cell Count
Cell Proliferation

Keywords

  • Aggregation
  • Human neural stem cell
  • Neurosphere
  • Proliferation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mori, H., Ninomiya, K., Kino-Oka, M., Shofuda, T., Islam, M. O., Yamasaki, M., ... Kanemura, Y. (2006). Effect of neurosphere size on the growth rate of human neural stem/progenitor cells. Journal of Neuroscience Research, 84(8), 1682-1691. https://doi.org/10.1002/jnr.21082

Effect of neurosphere size on the growth rate of human neural stem/progenitor cells. / Mori, Hideki; Ninomiya, Kazuaki; Kino-Oka, Masahiro; Shofuda, Tomoko; Islam, Mohammed Omedul; Yamasaki, Mami; Okano, Hideyuki; Taya, Masahito; Kanemura, Yonehiro.

In: Journal of Neuroscience Research, Vol. 84, No. 8, 12.2006, p. 1682-1691.

Research output: Contribution to journalArticle

Mori, H, Ninomiya, K, Kino-Oka, M, Shofuda, T, Islam, MO, Yamasaki, M, Okano, H, Taya, M & Kanemura, Y 2006, 'Effect of neurosphere size on the growth rate of human neural stem/progenitor cells', Journal of Neuroscience Research, vol. 84, no. 8, pp. 1682-1691. https://doi.org/10.1002/jnr.21082
Mori H, Ninomiya K, Kino-Oka M, Shofuda T, Islam MO, Yamasaki M et al. Effect of neurosphere size on the growth rate of human neural stem/progenitor cells. Journal of Neuroscience Research. 2006 Dec;84(8):1682-1691. https://doi.org/10.1002/jnr.21082
Mori, Hideki ; Ninomiya, Kazuaki ; Kino-Oka, Masahiro ; Shofuda, Tomoko ; Islam, Mohammed Omedul ; Yamasaki, Mami ; Okano, Hideyuki ; Taya, Masahito ; Kanemura, Yonehiro. / Effect of neurosphere size on the growth rate of human neural stem/progenitor cells. In: Journal of Neuroscience Research. 2006 ; Vol. 84, No. 8. pp. 1682-1691.
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