PLoS ONE (Jan 2013)

Derivation of neural stem cells from human adult peripheral CD34+ cells for an autologous model of neuroinflammation.

  • Tongguang Wang,
  • Elliot Choi,
  • Maria Chiara G Monaco,
  • Emilie Campanac,
  • Marie Medynets,
  • Thao Do,
  • Prashant Rao,
  • Kory R Johnson,
  • Abdel G Elkahloun,
  • Gloria Von Geldern,
  • Tory Johnson,
  • Sriram Subramaniam,
  • Dax A Hoffman,
  • Eugene Major,
  • Avindra Nath

DOI
https://doi.org/10.1371/journal.pone.0081720
Journal volume & issue
Vol. 8, no. 11
p. e81720

Abstract

Read online

Proinflammatory factors from activated T cells inhibit neurogenesis in adult animal brain and cultured human fetal neural stem cells (NSC). However, the role of inhibition of neurogenesis in human neuroinflammatory diseases is still uncertain because of the difficulty in obtaining adult NSC from patients. Recent developments in cell reprogramming suggest that NSC may be derived directly from adult fibroblasts. We generated NSC from adult human peripheral CD34+ cells by transfecting the cells with Sendai virus constructs containing Sox2, Oct3/4, c-Myc and Klf4. The derived NSC could be differentiated to glial cells and action potential firing neurons. Co-culturing NSC with activated autologous T cells or treatment with recombinant granzyme B caused inhibition of neurogenesis as indicated by decreased NSC proliferation and neuronal differentiation. Thus, we have established a unique autologous in vitro model to study the pathophysiology of neuroinflammatory diseases that has potential for usage in personalized medicine.