TY - JOUR TI - Secretome Analysis of Mesenchymal Stem Cell Factors Fostering Oligodendroglial Differentiation of Neural Stem Cells In Vivo AU - Samper Agrelo, Iria AU - Schira-Heinen, Jessica AU - Beyer, Felix AU - Groh, Janos AU - Bütermann, Christine AU - Estrada, Veronica AU - Poschmann, Gereon AU - Bribian, Ana AU - Jadasz, Janusz J. AU - Lopez-Mascaraque, Laura AU - Kremer, David AU - Martini, Rudolf AU - Müller, Hans Werner AU - Hartung, Hans Peter AU - Adjaye, James AU - Stühler, Kai AU - Küry, Patrick T2 - International Journal of Molecular Sciences AB - 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. DA - 2020/01// PY - 2020 DO - 10.3390/ijms21124350 DP - www.mdpi.com VL - 21 IS - 12 SP - 4350 LA - en UR - https://www.mdpi.com/1422-0067/21/12/4350 Y2 - 2020/06/23/17:42:42 KW - TIMP-1 KW - glial fate modulation KW - mesenchymal stem cells KW - myelin KW - neural stem cells KW - oligodendroglia KW - secretome KW - spinal cord KW - transplantation ER -