Open AccessMesenchymal Stem Cells Instruct Oligodendrogenic Fate Decision on Adult Neural Stem Cells
Author(s) -
Rivera Francisco J.,
CouillardDespres Sebastien,
Pedre Xiomara,
Ploetz Sonja,
Caioni Massimiliano,
Lois Carlos,
Bogdahn Ulrich,
Aigner Ludwig
Publication year - 2006
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2005-0614
Subject(s) - biology , olig2 , oligodendrocyte , mesenchymal stem cell , neural stem cell , neurogenesis , transplantation , stem cell , microbiology and biotechnology , glial fibrillary acidic protein , cellular differentiation , neurosphere , immunology , cell fate determination , adult stem cell , transcription factor , myelin , neuroscience , central nervous system , medicine , genetics , immunohistochemistry , gene
Adult stem cells reside in different tissues and organs of the adult organism. Among these cells are MSCs that are located in the adult bone marrow and NSCs that exist in the adult central nervous system (CNS). In transplantation experiments, MSCs demonstrated neuroprotective and neuroregenerative effects that were associated with functional improvements. The underlying mechanisms are largely unidentified. Here, we reveal that the interactions between adult MSCs and NSCs, mediated by soluble factors, induce oligodendrogenic fate decision in NSCs at the expense of astrogenesis. This was demonstrated (a) by an increase in the percentage of cells expressing the oligodendrocyte markers GalC and myelin basic protein, (b) by a reduction in the percentage of glial fibrillary acidic protein (GFAP)‐expressing cells, and (c) by the expression pattern of cell fate determinants specific for oligodendrogenic differentiation. Thus, it involved enhanced expression of the oligodendrogenic transcription factors Olig1, Olig2, and Nkx2.2 and diminished expression of Id2, an inhibitor of oligodendrogenic differentiation. Results of (a) 5‐bromo‐2′‐deoxyuridine pulse‐labeling of cells, (b) cell fate analysis, and (c) cell death/survival analysis suggested an inductive mechanism and excluded a selection process. A candidate factor screen excluded a number of growth factors, cytokines, and neurotrophins that have previously been shown to influence neurogenesis and neural differentiation from the oligodendrogenic activity derived from the MSCs. This work might have major implications for the development of future transplantation strategies for the treatment of degenerative diseases in the CNS.