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Forschungsdatenbank PMU-SQQUID

Bone morphogenetic proteins prevent bone marrow stromal cell-mediated oligodendroglial differentiation of transplanted adult neural progenitor cells in the injured spinal cord.
Sandner, B; Rivera, FJ; Caioni, M; Nicholson, L; Eckstein, V; Bogdahn, U; Aigner, L; Blesch, A; Weidner, N;
Stem Cell Res. 2013; 11(2):758-771
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Aigner Ludwig
Rivera Gomez-Barris Francisco J.

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-2xxx-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. (C) 2013 Elsevier B.V. All rights reserved.


Useful keywords (using NLM MeSH Indexing)

Animals

Bone Marrow Transplantation/methods*

Bone Morphogenetic Protein 2/metabolism*

Bone Morphogenetic Protein 4/metabolism*

Cell Differentiation/physiology

Female

Humans

Immunohistochemistry

Mesenchymal Stem Cell Transplantation/methods

Mesenchymal Stromal Cells/cytology*

Neural Stem Cells/cytology*

Neural Stem Cells/metabolism

Oligodendroglia/cytology*

Rats

Rats, Inbred F344

Rats, Sprague-Dawley

Rats, Transgenic

Spinal Cord Injuries/metabolism

Spinal Cord Injuries/pathology*

Spinal Cord Injuries/surgery