title: Bone morphogenetic proteins prevent bone marrow stromal cell-mediated oligodendroglial differentiation of transplanted adult neural progenitor cells in the injured spinal cord.
abstract: The loss of oligodendroglia and demyelination contributes to the lack of functional recovery after spinal cord injury. The transplantation of adult neural progenitor cells (NPCs) might be a promising strategy to replace oligodendroglia lost after injury, however only a very small proportion of grafted NPCs differentiate into oligodendroglia. The present study aimed to investigate whether co-transplantation of subventricular zone-derived NPCs with bone marrow stromal cells (BMSCs) will enhance oligodendroglial differentiation of NPCs. In vitro, oligodendroglial differentiation was strongly enhanced by co-cultivation of NPCs with BMSCs or BMSC-conditioned medium. For in vivo experiments, adult Fischer 344 rats underwent cervical dorsal funiculus transections, immediately followed by grafting of 5-bromo-2'-deoxyuridine (BrdU) pre-labeled syngeneic NPCs mixed with BMSCs isolated from adult bone marrow. Six weeks post-injury and grafting, BMSC-containing grafts filled the lesion cavity but did not enhance oligodendroglial differentiation of co-grafted NPCs. The failure of BMSCs to induce oligodendroglial differentiation in vivo coincided with a rapid upregulation of bone morphogenetic protein 2/4 (BMP2/4) around the injury site and in vitro data demonstrated that BMP2/4 can override the oligodendrogenic effects of BMSCs. Moreover, blocking BMP activity can rescue the effect of BMSCs on NPCs. Thus, neutralization of BMP or BMP signaling might be required to allow for BMSC-induced oligodendroglial differentiation of grafted NPCs in the injured spinal cord.
authors.affiliation: Department of Neurology, University of Regensburg, 93053 Regensburg, Germany.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Sandner
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Rivera
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Caioni
authors.forename: LaShae
authors.initials: L
authors.lastname: Nicholson
authors.forename: Volker
authors.initials: V
authors.lastname: Eckstein
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bogdahn
authors.forename: Ludwig
authors.initials: L
authors.lastname: Aigner
authors.forename: Armin
authors.initials: A
authors.lastname: Blesch
authors.forename: Norbert
authors.initials: N
authors.lastname: Weidner
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology* / Q000601:surgery
chemical_list: C525720:Bmp2 protein, rat; C525811:Bmp4 protein, rat; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4