Submitted on December 7, 2005
Accepted on May 30, 2006
Mesenchymal stem cells instruct oligodendrogenic fate decision on adult neural stem cells
Francisco J. Rivera 1,
Sebastien Couillard-Despres 2,
Xiomara Pedre 3,
Sonja Ploetz 2,
Massimiliano Caioni 3,
Carlos Lois 4,
Ulrich Bogdahn 3,
Ludwig Aigner 5*
1 Volkswagen-Foundation Research Group, University of Regensburg, Regensburg, Germany; Department of Neurology, University of Regensburg, Regensburg, Germany; Molecular and Cellular Biology and Neurosciences Program, Faculty of Science, Universidad de Chile, Santiago, Chile
2 Volkswagen-Foundation Research Group, University of Regensburg, Regensburg, Germany; Department of Neurology, University of Regensburg, Regensburg, Germany
3 Department of Neurology, University of Regensburg, Regensburg, Germany
4 Massachusetts Institute of Technology, Cambridge, Massachusetts
5 Volkswagen-Foundation Research Group, University of Regensburg, Regensburg, Germany; Molecular and Cellular Biology and Neurosciences Program, Faculty of Science, Universidad de Chile, Santiago, Chile
* To whom correspondence should be addressed. E-mail: Ludwig.Aigner{at}klinik.uni-regensburg.de.
 |
Abstract |
|---|
Adult stem cells reside in different tissues and organs of the adult organism. Among these cells are mesenchymal stem cells (MSCs) that are located in the adult bone marrow and neural stem cells (NSCs) that exist in the adult central nervous system (CNS). In transplantation experiments, MSCs demonstrated neuroprotective and neuro-regenerative 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 i) by an increase in the percentage of cells expressing the oligodendrocyte markers GalC and MBP, ii) by a reduction in the percentage of GFAP expressing cells and iii) 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 i) bromo-deoxyuridine (BrdU) pulse-labeling of cells, ii) cell fate analysis, and iii) 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.
