PMU-Autor/inn/en
Aigner LudwigAbstract
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.
Useful keywords (using NLM MeSH Indexing)
Cell Differentiation/genetics
Cell Differentiation/physiology
Cell Proliferation
Cell Survival/genetics
Cell Survival/physiology
Cells, Cultured
Coculture Techniques/methods
Culture Media/chemistry
Gene Expression Regulation/genetics
Glial Fibrillary Acidic Protein/genetics
Glial Fibrillary Acidic Protein/metabolism
Humans
Mesenchymal Stromal Cells/cytology*
Mesenchymal Stromal Cells/metabolism
Mesenchymal Stromal Cells/physiology
Neurons/cytology*
Neurons/metabolism
Oligodendroglia/cytology*
Oligodendroglia/metabolism
Reverse Transcriptase Polymerase Chain Reaction/methods
Transcription Factors/genetics
Transcription Factors/metabolism
Find related publications in this database (Keywords)
adult stem cells