LOTUS overexpression via ex vivo gene transduction further promotes recovery of motor function following human iPSC-NS/PC transplantation for contusive spinal cord injury

Shuhei Ito, Narihito Nagoshi, Yasuhiro Kamata, Kota Kojima, Satoshi Nori, Morio Matsumoto, Kohtaro Takei, Masaya Nakamura, Hideyuki Okano

Research output: Contribution to journalArticlepeer-review

Abstract

Functional recovery is still limited mainly due to several mechanisms, such as the activation of Nogo receptor-1 (NgR1) signaling, when human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PC) are transplanted for subacute spinal cord injury (SCI). We previously reported the neuroprotective and regenerative benefits of overexpression of lateral olfactory tract usher substance (LOTUS), an endogenous NgR1 antagonist, in the injured spinal cord using transgenic mice. Here, we evaluate the effects of lentiviral transduction of LOTUS gene into hiPSC-NS/PCs before transplantation in a mouse model of subacute SCI. The transduced LOTUS contributes to neurite extension, suppression of apoptosis, and secretion of neurotrophic factors in vitro. In vivo, the hiPSC-NS/PCs enhance the survival of grafted cells and enhance axonal extension of the transplanted cells, resulting in significant restoration of motor function following SCI. Therefore, the gene transduction of LOTUS in hiPSC-NS/PCs could be a promising adjunct for transplantation therapy for SCI.

Original languageEnglish
Pages (from-to)2703-2717
Number of pages15
JournalStem cell reports
Volume16
Issue number11
DOIs
Publication statusPublished - 2021 Nov 9

Keywords

  • axonal regrowth
  • ex vivo gene therapy
  • iPSC
  • LOTUS
  • motor function
  • Nogo receptor
  • regenerative medicine
  • spinal cord injury
  • transplantation

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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