Isolation and Characterization of Cerebellum-Derived Stem Cells in Poststroke Human Brain

Stem Cells Dev. 2019 Apr 15;28(8):528-542. doi: 10.1089/scd.2018.0232. Epub 2019 Mar 18.

Abstract

There is compelling evidence that the mature central nervous system (CNS) harbors stem cell populations outside conventional neurogenic regions. We previously demonstrated that brain pericytes (PCs) in both mouse and human exhibit multipotency to differentiate into various neural lineages following cerebral ischemia. PCs are found throughout the CNS, including cerebellum, but it remains unclear whether cerebellar PCs also form ischemia-induced multipotent stem cells (iSCs). In this study, we demonstrate that putative iSCs can be isolated from poststroke human cerebellum (cerebellar iSCs [cl-iSCs]). These cl-iSCs exhibited multipotency and differentiated into electrophysiologically active neurons. Neurogenic potential was also confirmed in single-cell suspensions. DNA microarray analysis revealed highly similar gene expression patterns between PCs and cl-iSCs, suggesting PC origin. Global gene expression comparison with cerebral iSCs revealed general similarity, but cl-iSCs differentially expressed certain cerebellum-specific genes. Thus, putative iSCs are present in poststroke cerebellum and possess region-specific traits, suggesting potential capacity to regenerate functional cerebellar neurons following ischemic stroke.

Keywords: cerebellum; human; ischemia; multipotent stem cells; pericytes; stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Brain / pathology
  • Brain Ischemia / pathology*
  • Brain Ischemia / rehabilitation
  • Cell Differentiation / physiology
  • Cell Separation
  • Cells, Cultured
  • Cerebellum / pathology*
  • Female
  • Humans
  • Male
  • Multipotent Stem Cells / pathology
  • Multipotent Stem Cells / physiology
  • Neural Stem Cells / pathology*
  • Neural Stem Cells / physiology*
  • Neurogenesis / physiology
  • Pericytes / pathology
  • Stroke / pathology*
  • Stroke Rehabilitation