title: Efficient derivation of multipotent neural stem/progenitor cells from non-human primate embryonic stem cells.
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.
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shimada
authors.forename: Yohei
authors.initials: Y
authors.lastname: Okada
authors.forename: Keiji
authors.initials: K
authors.lastname: Ibata
authors.forename: Hayao
authors.initials: H
authors.lastname: Ebise
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Ota
authors.forename: Ikuo
authors.initials: I
authors.lastname: Tomioka
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nomura
authors.forename: Takuji
authors.initials: T
authors.lastname: Maeda
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Kohda
authors.forename: Michisuke
authors.initials: M
authors.lastname: Yuzaki
authors.forename: Erika
authors.initials: E
authors.lastname: Sasaki
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
mesh_terms: D000818:Animals; D002144:Callithrix; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000502:physiology*; D004558:Electric Stimulation; D053595:Embryonic Stem Cells / Q000166:cytology*; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D046228:Microarray Analysis; D039902:Multipotent Stem Cells / Q000166:cytology*; D058953:Neural Stem Cells / Q000166:cytology*; D009457:Neuroglia / Q000166:cytology*; D009474:Neurons / Q000166:cytology*; D025341:Principal Component Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction