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Forschungsdatenbank PMU-SQQUID

Mesenchymal stem cells instruct oligodendrogenic fate decision on adult neural stem cells.
Rivera, FJ; Couillard-Despres, S; Pedre, X; Ploetz, S; Caioni, M; Lois, C; Bogdahn, U; Aigner, L;
Stem Cells. 2006; 24(10):2209-2219
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Aigner Ludwig
Couillard-Després Sébastien
Rivera Gomez-Barris Francisco J.

Abstract

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
transcription factor
somatic stem cells
real-time reverse transcription-polymerase chain reaction oligodendrocytes
enhanced green fluorescent protein
differentiation