Open AccessDerivation of Neural Stem Cells from Human Adult Peripheral CD34+ Cells for an Autologous Model of Neuroinflammation
Author(s) -
Tongguang Wang,
Elliot H. Choi,
Maria Chiara Monaco,
Emilie Campanac,
Marie Medynets,
Thao Do,
Prashant Rao,
Kory Johnson,
Abdel Elkahloun,
Gloria von Geldern,
Tory P. Johnson,
Sriram Subramaniam,
Dax A. Hoffman,
Eugene O. Major,
Avindra Nath
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0081720
Subject(s) - neurogenesis , neural stem cell , sox2 , neuroinflammation , biology , reprogramming , microbiology and biotechnology , neurosphere , stem cell , adult stem cell , cellular differentiation , immunology , cancer research , embryonic stem cell , cell , inflammation , genetics , gene , biochemistry
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.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom