TY  - JOUR
A1  - Samper Agrelo, Iria
A1  - Schira-Heinen, Jessica
A1  - Beyer, Felix
A1  - Groh, Janos
A1  - Bütermann, Christine
A1  - Estrada, Veronica
A1  - Poschmann, Gereon
A1  - Bribian, Ana
A1  - Jadasz, Janusz J.
A1  - Lopez-Mascaraque, Laura
A1  - Kremer, David
A1  - Martini, Rudolf
A1  - Müller, Hans Werner
A1  - Hartung, Hans Peter
A1  - Adjaye, James
A1  - Stühler, Kai
A1  - Küry, Patrick
T1  - Secretome analysis of mesenchymal stem cell factors fostering oligodendroglial differentiation of neural stem cells in vivo
JF  - International Journal of Molecular Sciences
N2  - 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.
KW  - neural stem cells
KW  - mesenchymal stem cells
KW  - transplantation
KW  - oligodendroglia
KW  - glial fate modulation
KW  - myelin
KW  - spinal cord
KW  - secretome
KW  - TIMP-1
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285465
SN  - 1422-0067
VL  - 21
IS  - 12
ER  - 
TY  - JOUR
A1  - Beyer, Felix
A1  - Jadasz, Janusz
A1  - Samper Agrelo, Iria
A1  - Schira‐Heinen, Jessica
A1  - Groh, Janos
A1  - Manousi, Anastasia
A1  - Bütermann, Christine
A1  - Estrada, Veronica
A1  - Reiche, Laura
A1  - Cantone, Martina
A1  - Vera, Julio
A1  - Viganò, Francesca
A1  - Dimou, Leda
A1  - Müller, Hans Werner
A1  - Hartung, Hans‐Peter
A1  - Küry, Patrick
T1  - Heterogeneous fate choice of genetically modulated adult neural stem cells in gray and white matter of the central nervous system
JF  - Glia
N2  - Apart from dedicated oligodendroglial progenitor cells, adult neural stem cells (aNSCs) can also give rise to new oligodendrocytes in the adult central nervous system (CNS). This process mainly confers myelinating glial cell replacement in pathological situations and can hence contribute to glial heterogeneity. Our previous studies demonstrated that the p57kip2 gene encodes an intrinsic regulator of glial fate acquisition and we here investigated to what degree its modulation can affect stem cell‐dependent oligodendrogenesis in different CNS environments. We therefore transplanted p57kip2 knockdown aNSCs into white and gray matter (WM and GM) regions of the mouse brain, into uninjured spinal cords as well as in the vicinity of spinal cord injuries and evaluated integration and differentiation in vivo. Our experiments revealed that under healthy conditions intrinsic suppression of p57kip2 as well as WM localization promote differentiation toward myelinating oligodendrocytes at the expense of astrocyte generation. Moreover, p57kip2 knockdown conferred a strong benefit on cell survival augmenting net oligodendrocyte generation. In the vicinity of hemisectioned spinal cords, the gene knockdown led to a similar induction of oligodendroglial features; however, newly generated oligodendrocytes appeared to suffer more from the hostile environment. This study contributes to our understanding of mechanisms of adult oligodendrogenesis and glial heterogeneity and further reveals critical factors when considering aNSC mediated cell replacement in injury and disease.
KW  - glial fate modulation
KW  - myelin
KW  - neural stem cell
KW  - p57kip2
KW  - regional heterogeneity
KW  - spinal cord injury
KW  - transplantation
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218566
VL  - 68
IS  - 2
SP  - 393
EP  - 406
ER  -