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Mesenchymal Stem Cells Instruct Oligodendrogenic Fate Decision on Adult Neural Stem Cells

Rivera, Francisco J. and Couillard-Despres, Sebastien and Pedre, Xiomara and Ploetz, Sonja and Caioni, Massimiliano and Lois, Carlos and Bogdahn, Ulrich and Aigner, Ludwig (2006) Mesenchymal Stem Cells Instruct Oligodendrogenic Fate Decision on Adult Neural Stem Cells. Stem Cells, 24 (10). pp. 2209-2219. ISSN 1066-5099. doi:10.1634/stemcells.2005-0614.

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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.

Item Type:Article
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Lois, Carlos0000-0002-7305-2317
Additional Information:© 2006 AlphaMed Press. Received December 7, 2005; accepted for publication May 30, 2006; first published online in STEM CELLS EXPRESS June 8, 2006. We thank Juergen Winkler, Beate Winner, and Norbert Weidner for critical and stimulating comments and Marco Mendez for statistical analysis support. We also thank Magdalena Götz for the Olig2 antibody and Norbert Weidner for the RIP antibody. This work was supported by Beca CONICYT (apoyo a realización de tesis doctoral, F.R.), CONICYT-DAAD (F.R.), DAAD (travel fellowship, L.A.), Volkswagen-Foundation, Hannover, Germany (L.A.), the ReForM program, School of Medicine, University of Regensburg (L.A.), and the Bayerische Forschungsstiftung, Munich, Germany (Grant PIZ 80/05, L.A.). The authors indicate no potential conflicts of interest.
Funding AgencyGrant Number
Comisión Nacional de Investigación Científica y Tecnológica (CONICYT)UNSPECIFIED
Deutscher Akademischer Austauschdienst (DAAD)UNSPECIFIED
Volkswagen FoundationUNSPECIFIED
University of RegensburgUNSPECIFIED
Bayerische ForschungsstiftungPIZ 80/05
Subject Keywords:Adult stem cells • Transcription factor • Somatic stem cells • Real-time reverse transcription-polymerase chain reaction • Oligodendrocytes • Enhanced green fluorescent protein Differentiation
Issue or Number:10
Record Number:CaltechAUTHORS:20181001-113520345
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Official Citation:Rivera, F. J., Couillard‐Despres, S. , Pedre, X. , Ploetz, S. , Caioni, M. , Lois, C. , Bogdahn, U. and Aigner, L. (2006), Mesenchymal Stem Cells Instruct Oligodendrogenic Fate Decision on Adult Neural Stem Cells. STEM CELLS, 24: 2209-2219. doi:10.1634/stemcells.2005-0614
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:90061
Deposited By: George Porter
Deposited On:05 Oct 2018 23:06
Last Modified:16 Nov 2021 00:40

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