title: Mesenchymal stem cells promote oligodendroglial differentiation in hippocampal slice cultures.
abstract: We have previously shown that soluble factors derived from mesenchymal stem cells (MSCs) induce oligodendrogenic fate and differentiation in adult rat neural progenitors (NPCs) in vitro. Here, we investigated if this pro-oligodendrogenic effect is maintained after cells have been transplanted onto rat hippocampal slice cultures, a CNS-organotypic environment. We first tested whether NPCs, that were pre-differentiated in vitro by MSC-derived conditioned medium, would generate oligodendrocytes after transplantation. This approach resulted in the loss of grafted NPCs, suggesting that oligodendroglial pre-differentiated cells could not integrate in the tissue and therefore did not survive grafting. However, when NPCs together with MSCs were transplanted in situ into hippocampal slice cultures, the grafted NPCs survived and the majority of them differentiated into oligodendrocytes. In contrast to the prevalent oligodendroglial differentiation in case of the NPC/MSC co-transplantation, naïve NPCs transplanted in the absence of MSCs differentiated predominantly into astrocytes. In summary, the pro-oligodendrogenic activity of MSCs was maintained only after co-transplantation into hippocampal slice cultures. Therefore, in the otherwise astrogenic milieu, MSCs established an oligodendrogenic niche for transplanted NPCs, and thus, co-transplantation of MSCs with NPCs might provide an attractive approach to re-myelinate the various regions of the diseased CNS.
authors.affiliation: Institute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, Salzburg, Salzburg, Austria.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Rivera
authors.forename: Florian A
authors.initials: FA
authors.lastname: Siebzehnrubl
authors.forename: Mahesh
authors.initials: M
authors.lastname: Kandasamy
authors.forename: Sebastien
authors.initials: S
authors.lastname: Couillard-Despres
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Caioni
authors.forename: Anne-Maria
authors.initials: AM
authors.lastname: Poehler
authors.forename: Benedikt
authors.initials: B
authors.lastname: Berninger
authors.forename: Beatrice
authors.initials: B
authors.lastname: Sandner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bogdahn
authors.forename: Magdalena
authors.initials: M
authors.lastname: Goetz
authors.forename: Ingmar
authors.initials: I
authors.lastname: Bluemcke
authors.forename: Norbert
authors.initials: N
authors.lastname: Weidner
authors.forename: Ludwig
authors.initials: L
authors.lastname: Aigner
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D005260:Female; D005269:Femur / Q000166:cytology; D006624:Hippocampus / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D013977:Tibia / Q000166:cytology
chemical_list: D000963:Antimetabolites; D001973:Bromodeoxyuridine