Chronic spinal cord injury functionally repaired by direct implantation of encapsulated hair-follicle-associated pluripotent (HAP) stem cells in a mouse model: Potential for clinical regenerative medicine

PLoS One. 2022 Jan 27;17(1):e0262755. doi: 10.1371/journal.pone.0262755. eCollection 2022.

Abstract

Chronic spinal cord injury (SCI) is a highly debilitating and recalcitrant disease with limited treatment options. Although various stem cell types have shown some clinical efficacy for injury repair they have not for SCI. Hair-follicle-associated pluripotent (HAP) stem cells have been shown to differentiate into neurons, Schwan cells, beating cardiomyocytes and many other type of cells, and have effectively regenerated acute spinal cord injury in mouse models. In the present report, HAP stem cells from C57BL/6J mice, encapsulated in polyvinylidene fluoride membranes (PFM), were implanted into the severed thoracic spinal cord of C57BL/6J or athymic nude mice in the early chronic phase. After implantation, HAP stem cells differentiated to neurons, astrocytes and oligodendrocytes in the regenerated thoracic spinal cord of C57BL/6J and nude mice. Quantitative motor function analysis, with the Basso Mouse Scale for Locomotion (BMS) score, demonstrated a significant functional improvement in the HAP-stem-cell-implanted mice, compared to non-implanted mice. HAP stem cells have critical advantages over other stem cells: they do not develop teratomas; do not loose differentiation ability when cryopreserved and thus are bankable; are autologous, readily obtained from anyone; and do not require genetic manipulation. HAP stem cells therefore have greater clinical potential for SCI repair than induced pluripotent stem cells (iPSCs), neuronal stem cells (NSCs)/neural progenitor cells (NPCs) or embryonic stem cells (ESCs). The present report demonstrates future clinical potential of HAP-stem-cell repair of chronic spinal cord injury, currently a recalcitrant disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Fluorocarbon Polymers / metabolism
  • Hair Follicle / cytology*
  • Hair Follicle / metabolism
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mice, Transgenic
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / physiology
  • Nestin / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neurons / cytology
  • Neurons / metabolism
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • Polyvinyls / metabolism
  • Regenerative Medicine / methods
  • Spinal Cord / metabolism
  • Spinal Cord / physiopathology
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / physiopathology*
  • Spinal Cord Injuries / therapy*
  • Spinal Cord Regeneration / physiology*

Substances

  • Fluorocarbon Polymers
  • Nestin
  • Polyvinyls
  • polyvinylidene fluoride

Grants and funding

The authors disclosed receipt of the following financial support for the research and authorship of this article: This work was partially supported by JSPS KAKENHI Grant Number JP19K17815, Kitasato University Research Grant for Young Researchers and the Parents Association Grant of Kitasato University, School of Medicine (to K. Obara). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.