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Article

Secretome Analysis of Mesenchymal Stem Cell Factors Fostering Oligodendroglial Differentiation of Neural Stem Cells In Vivo

1
Department of Neurology, Medical Faculty, Heinrich-Heine-University, D-40225 Düsseldorf, Germany
2
Institute for Biochemistry, University of Erlangen-Nürnberg, 91054 Erlangen, Germany
3
Department of Neurology, Section of Developmental Neurobiology, University Hospital Würzburg, D-97080 Würzburg, Germany
4
Institute for Molecular Medicine, Proteome Research, Medical Faculty, Heinrich-Heine-University, D-40225 Düsseldorf, Germany
5
Departamento de Neurobiología Molecular, Celular y del Desarrollo, Instituto Cajal-CSIC, 28002 Madrid, Spain
6
Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine-University, D-40225 Düsseldorf, Germany
7
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. View Full-Text
Keywords: neural stem cells; mesenchymal stem cells; transplantation; oligodendroglia; glial fate modulation; myelin; spinal cord; secretome; TIMP-1 neural stem cells; mesenchymal stem cells; transplantation; oligodendroglia; glial fate modulation; myelin; spinal cord; secretome; TIMP-1
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MDPI and ACS Style

Samper Agrelo, I.; Schira-Heinen, J.; Beyer, F.; Groh, J.; Bütermann, C.; Estrada, V.; Poschmann, G.; Bribian, A.; Jadasz, J.J.; Lopez-Mascaraque, L.; Kremer, D.; Martini, R.; Müller, H.W.; Hartung, H.P.; Adjaye, J.; Stühler, K.; Küry, P. Secretome Analysis of Mesenchymal Stem Cell Factors Fostering Oligodendroglial Differentiation of Neural Stem Cells In Vivo. Int. J. Mol. Sci. 2020, 21, 4350. https://doi.org/10.3390/ijms21124350

AMA Style

Samper Agrelo I, Schira-Heinen J, Beyer F, Groh J, Bütermann C, Estrada V, Poschmann G, Bribian A, Jadasz JJ, Lopez-Mascaraque L, Kremer D, Martini R, Müller HW, Hartung HP, Adjaye J, Stühler K, Küry P. Secretome Analysis of Mesenchymal Stem Cell Factors Fostering Oligodendroglial Differentiation of Neural Stem Cells In Vivo. International Journal of Molecular Sciences. 2020; 21(12):4350. https://doi.org/10.3390/ijms21124350

Chicago/Turabian Style

Samper Agrelo, Iria, Jessica Schira-Heinen, Felix Beyer, Janos Groh, Christine Bütermann, Veronica Estrada, Gereon Poschmann, Ana Bribian, Janusz J. Jadasz, Laura Lopez-Mascaraque, David Kremer, Rudolf Martini, Hans W. Müller, Hans P. Hartung, James Adjaye, Kai Stühler, and Patrick Küry. 2020. "Secretome Analysis of Mesenchymal Stem Cell Factors Fostering Oligodendroglial Differentiation of Neural Stem Cells In Vivo" International Journal of Molecular Sciences 21, no. 12: 4350. https://doi.org/10.3390/ijms21124350

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