Pretreatment with a γ-Secretase Inhibitor Prevents Tumor-like Overgrowth in Human iPSC-Derived Transplants for Spinal Cord Injury

Toshiki Okubo, Akio Iwanami, Jun Kohyama, Go Itakura, Soya Kawabata, Yuichiro Nishiyama, Keiko Sugai, Masahiro Ozaki, Tsuyoshi Iida, Kohei Matsubayashi, Morio Matsumoto, Masaya Nakamura, Hideyuki Okano

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) are considered to be a promising cell source for cell-based interventions that target CNS disorders. We previously reported that transplanting certain hiPSC-NS/PCs in the spinal cord results in tumor-like overgrowth of hiPSC-NS/PCs and subsequent deterioration of motor function. Remnant immature cells should be removed or induced into more mature cell types to avoid adverse effects of hiPSC-NS/PC transplantation. Because Notch signaling plays a role in maintaining NS/PCs, we evaluated the effects of γ-secretase inhibitor (GSI) and found that pretreating hiPSC-NS/PCs with GSI promoted neuronal differentiation and maturation in vitro, and GSI pretreatment also reduced the overgrowth of transplanted hiPSC-NS/PCs and inhibited the deterioration of motor function in vivo. These results indicate that pretreatment with hiPSC-NS/PCs decreases the proliferative capacity of transplanted hiPSC-NS/PCs, triggers neuronal commitment, and improves the safety of hiPSC-based approaches in regenerative medicine.

Original languageEnglish
Pages (from-to)649-663
Number of pages15
JournalStem cell reports
Volume7
Issue number4
DOIs
Publication statusPublished - 2016 Oct 11

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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