Roles of ES cell-derived gliogenic neural stem/progenitor cells in functional recovery after spinal cord injury

Gentaro Kumagai, Yohei Okada, Junichi Yamane, Narihito Nagoshi, Kazuya Kitamura, Masahiko Mukaino, Osahiko Tsuji, Kanehiro Fujiyoshi, Hiroyuki Katoh, Seiji Okada, Shinsuke Shibata, Yumi Matsuzaki, Satoshi Toh, Yoshiaki Toyama, Masaya Nakamura, Hideyuki Okano

Research output: Contribution to journalArticle

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Abstract

Transplantation of neural stem/progenitor cells (NS/PCs) following the sub-acute phase of spinal cord injury (SCI) has been shown to promote functional recovery in rodent models. However, the types of cells most effective for treating SCI have not been clarified. Taking advantage of our recently established neurosphere-based culture system of ES cell-derived NS/PCs, in which primary neurospheres (PNS) and passaged secondary neurospheres (SNS) exhibit neurogenic and gliogenic potentials, respectively, here we examined the distinct effects of transplanting neurogenic and gliogenic NS/PCs on the functional recovery of a mouse model of SCI. ES cell-derived PNS and SNS transplanted 9 days after contusive injury at the Th10 level exhibited neurogenic and gliogenic differentiation tendencies, respectively, similar to those seen in vitro. Interestingly, transplantation of the gliogenic SNS, but not the neurogenic PNS, promoted axonal growth, remyelination, and angiogenesis, and resulted in significant locomotor functional recovery after SCI. These findings suggest that gliogenic NS/PCs are effective for promoting the recovery from SCI, and provide essential insight into the mechanisms through which cellular transplantation leads to functional improvement after SCI.

Original languageEnglish
Article numbere7706
JournalPloS one
Volume4
Issue number11
DOIs
Publication statusPublished - 06-11-2009

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Neural Stem Cells
Stem cells
Spinal Cord Injuries
spinal cord
stem cells
Stem Cells
Recovery
Transplantation
cells
Cell culture
Rodentia
angiogenesis
rodents
animal models
Wounds and Injuries
Growth

All Science Journal Classification (ASJC) codes

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

Cite this

Kumagai, Gentaro ; Okada, Yohei ; Yamane, Junichi ; Nagoshi, Narihito ; Kitamura, Kazuya ; Mukaino, Masahiko ; Tsuji, Osahiko ; Fujiyoshi, Kanehiro ; Katoh, Hiroyuki ; Okada, Seiji ; Shibata, Shinsuke ; Matsuzaki, Yumi ; Toh, Satoshi ; Toyama, Yoshiaki ; Nakamura, Masaya ; Okano, Hideyuki. / Roles of ES cell-derived gliogenic neural stem/progenitor cells in functional recovery after spinal cord injury. In: PloS one. 2009 ; Vol. 4, No. 11.
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abstract = "Transplantation of neural stem/progenitor cells (NS/PCs) following the sub-acute phase of spinal cord injury (SCI) has been shown to promote functional recovery in rodent models. However, the types of cells most effective for treating SCI have not been clarified. Taking advantage of our recently established neurosphere-based culture system of ES cell-derived NS/PCs, in which primary neurospheres (PNS) and passaged secondary neurospheres (SNS) exhibit neurogenic and gliogenic potentials, respectively, here we examined the distinct effects of transplanting neurogenic and gliogenic NS/PCs on the functional recovery of a mouse model of SCI. ES cell-derived PNS and SNS transplanted 9 days after contusive injury at the Th10 level exhibited neurogenic and gliogenic differentiation tendencies, respectively, similar to those seen in vitro. Interestingly, transplantation of the gliogenic SNS, but not the neurogenic PNS, promoted axonal growth, remyelination, and angiogenesis, and resulted in significant locomotor functional recovery after SCI. These findings suggest that gliogenic NS/PCs are effective for promoting the recovery from SCI, and provide essential insight into the mechanisms through which cellular transplantation leads to functional improvement after SCI.",
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Kumagai, G, Okada, Y, Yamane, J, Nagoshi, N, Kitamura, K, Mukaino, M, Tsuji, O, Fujiyoshi, K, Katoh, H, Okada, S, Shibata, S, Matsuzaki, Y, Toh, S, Toyama, Y, Nakamura, M & Okano, H 2009, 'Roles of ES cell-derived gliogenic neural stem/progenitor cells in functional recovery after spinal cord injury', PloS one, vol. 4, no. 11, e7706. https://doi.org/10.1371/journal.pone.0007706

Roles of ES cell-derived gliogenic neural stem/progenitor cells in functional recovery after spinal cord injury. / Kumagai, Gentaro; Okada, Yohei; Yamane, Junichi; Nagoshi, Narihito; Kitamura, Kazuya; Mukaino, Masahiko; Tsuji, Osahiko; Fujiyoshi, Kanehiro; Katoh, Hiroyuki; Okada, Seiji; Shibata, Shinsuke; Matsuzaki, Yumi; Toh, Satoshi; Toyama, Yoshiaki; Nakamura, Masaya; Okano, Hideyuki.

In: PloS one, Vol. 4, No. 11, e7706, 06.11.2009.

Research output: Contribution to journalArticle

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AU - Kumagai, Gentaro

AU - Okada, Yohei

AU - Yamane, Junichi

AU - Nagoshi, Narihito

AU - Kitamura, Kazuya

AU - Mukaino, Masahiko

AU - Tsuji, Osahiko

AU - Fujiyoshi, Kanehiro

AU - Katoh, Hiroyuki

AU - Okada, Seiji

AU - Shibata, Shinsuke

AU - Matsuzaki, Yumi

AU - Toh, Satoshi

AU - Toyama, Yoshiaki

AU - Nakamura, Masaya

AU - Okano, Hideyuki

PY - 2009/11/6

Y1 - 2009/11/6

N2 - Transplantation of neural stem/progenitor cells (NS/PCs) following the sub-acute phase of spinal cord injury (SCI) has been shown to promote functional recovery in rodent models. However, the types of cells most effective for treating SCI have not been clarified. Taking advantage of our recently established neurosphere-based culture system of ES cell-derived NS/PCs, in which primary neurospheres (PNS) and passaged secondary neurospheres (SNS) exhibit neurogenic and gliogenic potentials, respectively, here we examined the distinct effects of transplanting neurogenic and gliogenic NS/PCs on the functional recovery of a mouse model of SCI. ES cell-derived PNS and SNS transplanted 9 days after contusive injury at the Th10 level exhibited neurogenic and gliogenic differentiation tendencies, respectively, similar to those seen in vitro. Interestingly, transplantation of the gliogenic SNS, but not the neurogenic PNS, promoted axonal growth, remyelination, and angiogenesis, and resulted in significant locomotor functional recovery after SCI. These findings suggest that gliogenic NS/PCs are effective for promoting the recovery from SCI, and provide essential insight into the mechanisms through which cellular transplantation leads to functional improvement after SCI.

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