Secretome Analysis of Mesenchymal Stem Cell Factors Fostering Oligodendroglial Differentiation of Neural Stem Cells In Vivo
Department of Neurology, Medical Faculty, Heinrich-Heine-University, D-40225 Düsseldorf, Germany
Institute for Biochemistry, University of Erlangen-Nürnberg, 91054 Erlangen, Germany
Department of Neurology, Section of Developmental Neurobiology, University Hospital Würzburg, D-97080 Würzburg, Germany
Institute for Molecular Medicine, Proteome Research, Medical Faculty, Heinrich-Heine-University, D-40225 Düsseldorf, Germany
Departamento de Neurobiología Molecular, Celular y del Desarrollo, Instituto Cajal-CSIC, 28002 Madrid, Spain
Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine-University, D-40225 Düsseldorf, Germany
Molecular Proteomics Laboratory (MPL), Biologisch-Medizinisches Forschungszentrum (BMFZ), Heinrich-Heine-University, D-40225 Düsseldorf, Germany
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(12), 4350; https://doi.org/10.3390/ijms21124350
Received: 25 May 2020 / Revised: 14 June 2020 / Accepted: 16 June 2020 / Published: 18 June 2020
(This article belongs to the Special Issue Cellular Secretomes)
Mesenchymal stem cell (MSC)-secreted factors have been shown to significantly promote oligodendrogenesis from cultured primary adult neural stem cells (aNSCs) and oligodendroglial precursor cells (OPCs). Revealing underlying mechanisms of how aNSCs can be fostered to differentiate into a specific cell lineage could provide important insights for the establishment of novel neuroregenerative treatment approaches aiming at myelin repair. However, the nature of MSC-derived differentiation and maturation factors acting on the oligodendroglial lineage has not been identified thus far. In addition to missing information on active ingredients, the degree to which MSC-dependent lineage instruction is functional in vivo also remains to be established. We here demonstrate that MSC-derived factors can indeed stimulate oligodendrogenesis and myelin sheath generation of aNSCs transplanted into different rodent central nervous system (CNS) regions, and furthermore, we provide insights into the underlying mechanism on the basis of a comparative mass spectrometry secretome analysis. We identified a number of secreted proteins known to act on oligodendroglia lineage differentiation. Among them, the tissue inhibitor of metalloproteinase type 1 (TIMP-1) was revealed to be an active component of the MSC-conditioned medium, thus validating our chosen secretome approach.