Pre-Evaluated Safe Human iPSC-Derived Neural Stem Cells Promote Functional Recovery after Spinal Cord Injury in Common Marmoset without Tumorigenicity

Yoshiomi Kobayashi, Yohei Okada, Go Itakura, Hiroki Iwai, Soraya Nishimura, Akimasa Yasuda, Satoshi Nori, Keigo Hikishima, Tsunehiko Konomi, Kanehiro Fujiyoshi, Osahiko Tsuji, Yoshiaki Toyama, Shinya Yamanaka, Masaya Nakamura, Hideyuki Okano

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

Murine and human iPSC-NS/PCs (induced pluripotent stem cell-derived neural stem/progenitor cells) promote functional recovery following transplantation into the injured spinal cord in rodents. However, for clinical applicability, it is critical to obtain proof of the concept regarding the efficacy of grafted human iPSC-NS/PCs (hiPSC-NS/PCs) for the repair of spinal cord injury (SCI) in a non-human primate model. This study used a pre-evaluated "safe" hiPSC-NS/PC clone and an adult common marmoset (Callithrix jacchus) model of contusive SCI. SCI was induced at the fifth cervical level (C5), followed by transplantation of hiPSC-NS/PCs at 9 days after injury. Behavioral analyses were performed from the time of the initial injury until 12 weeks after SCI. Grafted hiPSC-NS/PCs survived and differentiated into all three neural lineages. Furthermore, transplantation of hiPSC-NS/PCs enhanced axonal sparing/regrowth and angiogenesis, and prevented the demyelination after SCI compared with that in vehicle control animals. Notably, no tumor formation occurred for at least 12 weeks after transplantation. Quantitative RT-PCR showed that mRNA expression levels of human neurotrophic factors were significantly higher in cultured hiPSC-NS/PCs than in human dermal fibroblasts (hDFs). Finally, behavioral tests showed that hiPSC-NS/PCs promoted functional recovery after SCI in the common marmoset. Taken together, these results indicate that pre-evaluated safe hiPSC-NS/PCs are a potential source of cells for the treatment of SCI in the clinic.

Original languageEnglish
Article numbere52787
JournalPLoS One
Volume7
Issue number12
DOIs
Publication statusPublished - 2012 Dec 27

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Callithrix
Callithrix jacchus
Neural Stem Cells
Stem cells
Spinal Cord Injuries
spinal cord
stem cells
Recovery
Transplantation
Induced Pluripotent Stem Cells
Stem Cells
Nerve Growth Factors
neurotrophins
Fibroblasts
Wounds and Injuries
Demyelinating Diseases
angiogenesis
regrowth
Tumors
Primates

ASJC Scopus subject areas

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

Cite this

Pre-Evaluated Safe Human iPSC-Derived Neural Stem Cells Promote Functional Recovery after Spinal Cord Injury in Common Marmoset without Tumorigenicity. / Kobayashi, Yoshiomi; Okada, Yohei; Itakura, Go; Iwai, Hiroki; Nishimura, Soraya; Yasuda, Akimasa; Nori, Satoshi; Hikishima, Keigo; Konomi, Tsunehiko; Fujiyoshi, Kanehiro; Tsuji, Osahiko; Toyama, Yoshiaki; Yamanaka, Shinya; Nakamura, Masaya; Okano, Hideyuki.

In: PLoS One, Vol. 7, No. 12, e52787, 27.12.2012.

Research output: Contribution to journalArticle

Kobayashi, Y, Okada, Y, Itakura, G, Iwai, H, Nishimura, S, Yasuda, A, Nori, S, Hikishima, K, Konomi, T, Fujiyoshi, K, Tsuji, O, Toyama, Y, Yamanaka, S, Nakamura, M & Okano, H 2012, 'Pre-Evaluated Safe Human iPSC-Derived Neural Stem Cells Promote Functional Recovery after Spinal Cord Injury in Common Marmoset without Tumorigenicity', PLoS One, vol. 7, no. 12, e52787. https://doi.org/10.1371/journal.pone.0052787
Kobayashi, Yoshiomi ; Okada, Yohei ; Itakura, Go ; Iwai, Hiroki ; Nishimura, Soraya ; Yasuda, Akimasa ; Nori, Satoshi ; Hikishima, Keigo ; Konomi, Tsunehiko ; Fujiyoshi, Kanehiro ; Tsuji, Osahiko ; Toyama, Yoshiaki ; Yamanaka, Shinya ; Nakamura, Masaya ; Okano, Hideyuki. / Pre-Evaluated Safe Human iPSC-Derived Neural Stem Cells Promote Functional Recovery after Spinal Cord Injury in Common Marmoset without Tumorigenicity. In: PLoS One. 2012 ; Vol. 7, No. 12.
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