Human Spinal Oligodendrogenic Neural Progenitor Cells Promote Functional Recovery After Spinal Cord Injury by Axonal Remyelination and Tissue Sparing

Narihito Nagoshi, Mohamad Khazaei, Jan Eric Ahlfors, Christopher S. Ahuja, Satoshi Nori, Jian Wang, Shinsuke Shibata, Michael G. Fehlings

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Cell transplantation therapy utilizing neural precursor cells (NPCs) is a conceptually attractive strategy for traumatic spinal cord injury (SCI) to replace lost cells, remyelinate denuded host axons and promote tissue sparing. However, the number of mature oligodendrocytes that differentiate from typical NPCs remains limited. Herein, we describe a novel approach to bias the differentiation of directly reprogrammed human NPCs (drNPCs) toward a more oligodendrogenic fate (oNPCs) while preserving their tripotency. The oNPCs derived from different lines of human NPCs showed similar characteristics in vitro. To assess the in vivo efficacy of this approach, we used oNPCs derived from drNPCs and transplanted them into a SCI model in immunodeficient Rowett Nude (RNU) rats. The transplanted cells showed significant migration along the rostrocaudal axis and proportionally greater differentiation into oligodendrocytes. These cells promoted perilesional tissue sparing and axonal remyelination, which resulted in recovery of motor function. Moreover, after transplantation of the oNPCs into intact spinal cords of immunodeficient NOD/SCID mice, we detected no evidence of tumor formation even after 5 months of observation. Thus, biasing drNPC differentiation along an oligodendroglial lineage represents a promising approach to promote tissue sparing, axonal remyelination, and neural repair after traumatic SCI. Stem Cells Translational Medicine 2018;7:806–818.

Original languageEnglish
Pages (from-to)806-818
Number of pages13
JournalStem cells translational medicine
Volume7
Issue number11
DOIs
Publication statusPublished - 2018 Nov 1

Fingerprint

Spinal Cord Injuries
Stem Cells
Oligodendroglia
Nude Rats
Inbred NOD Mouse
Translational Medical Research
SCID Mice
Cell Transplantation
Recovery of Function
Cell- and Tissue-Based Therapy
Axons
Spinal Cord
Transplantation
Observation
Neoplasms

Keywords

  • Oligodendrocytes
  • Oligodendrogenic neural progenitor cells
  • Regeneration
  • Remyelination
  • Spinal cord injury
  • Stem cells

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Human Spinal Oligodendrogenic Neural Progenitor Cells Promote Functional Recovery After Spinal Cord Injury by Axonal Remyelination and Tissue Sparing. / Nagoshi, Narihito; Khazaei, Mohamad; Ahlfors, Jan Eric; Ahuja, Christopher S.; Nori, Satoshi; Wang, Jian; Shibata, Shinsuke; Fehlings, Michael G.

In: Stem cells translational medicine, Vol. 7, No. 11, 01.11.2018, p. 806-818.

Research output: Contribution to journalArticle

Nagoshi, Narihito ; Khazaei, Mohamad ; Ahlfors, Jan Eric ; Ahuja, Christopher S. ; Nori, Satoshi ; Wang, Jian ; Shibata, Shinsuke ; Fehlings, Michael G. / Human Spinal Oligodendrogenic Neural Progenitor Cells Promote Functional Recovery After Spinal Cord Injury by Axonal Remyelination and Tissue Sparing. In: Stem cells translational medicine. 2018 ; Vol. 7, No. 11. pp. 806-818.
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