A robust culture system to generate neural progenitors with gliogenic competence from clinically relevant induced pluripotent stem cells for treatment of spinal cord injury

Yasuhiro Kamata, Miho Isoda, Tsukasa Sanosaka, Reo Shibata, Shuhei Ito, Toshiki Okubo, Munehisa Shinozaki, Mitsuhiro Inoue, Ikuko Koya, Shinsuke Shibata, Tomoko Shindo, Morio Matsumoto, Masaya Nakamura, Hideyuki Okano, Narihito Nagoshi, Jun Kohyama

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Cell-based therapy targeting spinal cord injury (SCI) is an attractive approach to promote functional recovery by replacing damaged tissue. We and other groups have reported the effectiveness of transplanting neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) in SCI animal models for neuronal replacement. Glial replacement is an additional approach for tissue repair; however, the lack of robust procedures to drive iPSCs into NS/PCs which can produce glial cells has hindered the development of glial cell transplantation for the restoration of neuronal functions after SCI. Here, we established a method to generate NS/PCs with gliogenic competence (gNS/PCs) optimized for clinical relevance and utilized them as a source of therapeutic NS/PCs for SCI. We could successfully generate gNS/PCs from clinically relevant hiPSCs, which efficiently produced astrocytes and oligodendrocytes in vitro. We also performed comparison between gNS/PCs and neurogenic NS/PCs based on single cell RNA-seq analysis and found that gNS/PCs were distinguished by expression of several transcription factors including HEY2 and NFIB. After gNS/PC transplantation, the graft did not exhibit tumor-like tissue formation, indicating the safety of them as a source of cell therapy. Importantly, the gNS/PCs triggered functional recovery in an SCI animal model, with remyelination of demyelinated axons and improved motor function. Given the inherent safety of gNS/PCs and favorable outcomes observed after their transplantation, cell-based medicine using the gNS/PCs-induction procedure described here together with clinically relevant iPSCs is realistic and would be beneficial for SCI patients.

Original languageEnglish
Pages (from-to)398-413
Number of pages16
JournalStem Cells Translational Medicine
Volume10
Issue number3
DOIs
Publication statusPublished - 2021 Mar

Keywords

  • HLA-homo
  • induced pluripotent stem cells
  • neural stem progenitor cells
  • oligodendrocyte
  • remyelination
  • spinal cord injury

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'A robust culture system to generate neural progenitors with gliogenic competence from clinically relevant induced pluripotent stem cells for treatment of spinal cord injury'. Together they form a unique fingerprint.

Cite this