Efficient Derivation of Multipotent Neural Stem/Progenitor Cells from Non-Human Primate Embryonic Stem Cells

Hiroko Shimada, Yohei Okada, Keiji Ibata, Hayao Ebise, Shin ichi Ota, Ikuo Tomioka, Toshihiro Nomura, Takuji Maeda, Kazuhisa Kohda, Michisuke Yuzaki, Erika Sasaki, Masaya Nakamura, Hideyuki Okano

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The common marmoset (Callithrix jacchus) is a small New World primate that has been used as a non-human primate model for various biomedical studies. We previously demonstrated that transplantation of neural stem/progenitor cells (NS/PCs) derived from mouse and human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) promote functional locomotor recovery of mouse spinal cord injury models. However, for the clinical application of such a therapeutic approach, we need to evaluate the efficacy and safety of pluripotent stem cell-derived NS/PCs not only by xenotransplantation, but also allotransplantation using non-human primate models to assess immunological rejection and tumorigenicity. In the present study, we established a culture method to efficiently derive NS/PCs as neurospheres from common marmoset ESCs. Marmoset ESC-derived neurospheres could be passaged repeatedly and showed sequential generation of neurons and astrocytes, similar to that of mouse ESC-derived NS/PCs, and gave rise to functional neurons as indicated by calcium imaging. Although marmoset ESC-derived NS/PCs could not differentiate into oligodendrocytes under default culture conditions, these cells could abundantly generate oligodendrocytes by incorporating additional signals that recapitulate in vivo neural development. Moreover, principal component analysis of microarray data demonstrated that marmoset ESC-derived NS/PCs acquired similar gene expression profiles to those of fetal brain-derived NS/PCs by repeated passaging. Therefore, marmoset ESC-derived NS/PCs may be useful not only for accurate evaluation by allotransplantation of NS/PCs into non-human primate models, but are also applicable to analysis of iPSCs established from transgenic disease model marmosets.

Original languageEnglish
Article numbere49469
JournalPLoS One
Volume7
Issue number11
DOIs
Publication statusPublished - 2012 Nov 14

Fingerprint

Multipotent Stem Cells
Neural Stem Cells
Callithrix
embryonic stem cells
Embryonic Stem Cells
Stem cells
Primates
stem cells
Stem Cells
Callitrichidae
Induced Pluripotent Stem Cells
Oligodendroglia
Callithrix jacchus
Neurons
Pluripotent Stem Cells
Heterologous Transplantation
animal models
Principal Component Analysis
Spinal Cord Injuries
Transcriptome

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Efficient Derivation of Multipotent Neural Stem/Progenitor Cells from Non-Human Primate Embryonic Stem Cells. / Shimada, Hiroko; Okada, Yohei; Ibata, Keiji; Ebise, Hayao; Ota, Shin ichi; Tomioka, Ikuo; Nomura, Toshihiro; Maeda, Takuji; Kohda, Kazuhisa; Yuzaki, Michisuke; Sasaki, Erika; Nakamura, Masaya; Okano, Hideyuki.

In: PLoS One, Vol. 7, No. 11, e49469, 14.11.2012.

Research output: Contribution to journalArticle

Shimada, H, Okada, Y, Ibata, K, Ebise, H, Ota, SI, Tomioka, I, Nomura, T, Maeda, T, Kohda, K, Yuzaki, M, Sasaki, E, Nakamura, M & Okano, H 2012, 'Efficient Derivation of Multipotent Neural Stem/Progenitor Cells from Non-Human Primate Embryonic Stem Cells', PLoS One, vol. 7, no. 11, e49469. https://doi.org/10.1371/journal.pone.0049469
Shimada, Hiroko ; Okada, Yohei ; Ibata, Keiji ; Ebise, Hayao ; Ota, Shin ichi ; Tomioka, Ikuo ; Nomura, Toshihiro ; Maeda, Takuji ; Kohda, Kazuhisa ; Yuzaki, Michisuke ; Sasaki, Erika ; Nakamura, Masaya ; Okano, Hideyuki. / Efficient Derivation of Multipotent Neural Stem/Progenitor Cells from Non-Human Primate Embryonic Stem Cells. In: PLoS One. 2012 ; Vol. 7, No. 11.
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