25-07-08(12:12:32)
Authors:
Sandner B, Rivera F, Caioni M, Aigner L, Weidner N
Institutions:
Dept. of Neurology, University of Regensburg, Germany, 93053.
Title of abstract : Co-transplantation of adult neural progenitor cells with cells of mesenchymal origin for oligodendrogia replacement after spinal cord injury.
Abstract text:
The loss of oligodendroglia and the resulting demyelination represents one of the key problems inhibiting recovery from spinal cord injury. The transplantation of adult neural progenitor cells (NPC) might be a promising oligodendroglia replacement strategy. After transplantation into the acutely injured spinal cord, NPC readily survive, however, only a relatively minor proportion of grafted NPC differentiates into oligodendroglia. In vitro, oligodendroglial differentiation can be strongly enhanced by co-cultivating mesenchymal stem cells (MSC) with NPC. The aim of the present study was to investigate whether co-transplantation of NPC with MSC into the injured spinal cord will significantly enhance oligodendroglial differentiation of NPC in vivo. For both syngenic cell isolation and the in vivo experiments adult female Fischer 344 rats were taken. NPC were isolated from the subventricular zone, MSC from the femur and fibroblasts (FF) from skin biopsies. Before transplantation, NPC were prelabeled with BrdU. Rats received cervical tungsten wire knife dorsal column transections. Immediately thereafter, a) 0.6 x 105 MSC/µl (MSC), b) 1.8 x 105 NPC/µl (NPC), c) 0.3 x 105 MSC/µl + 1.2 x 105 NPC/µl (MSC/NPC) or 0.3 x 105 FF/µl + 1.2 x 105 NPC/µl (FF/NPC) were transplanted directly into the lesion site. Six weeks post-operatively, only FF or MSC containing grafts replaced the cystic lesion defect. Vast detection of BrdU positive nuclei indicated robust survival of NPC within respective grafts. Surprisingly, the quantification of immunohistochemical markers for oligodendroglia, namely APC and GST-pi showed a shift of NPC differentiation towards an oligodendroglial phenotype in FF/NPC grafts, but not in MSC/NPC grafts. Furthermore, it seems that the endogenous gliogenesis is also shifted towards an oligodendroglial phenotype, which has to be confirmed by thorough quantitative analysis. Ongoing studies investigate whether the promotion of oligodendroglial differentiation enhances remyelination within and outside of FF/NPC co-grafts. At this point, the combination of NPC with fibroblasts rather than MSC induces oligodendroglial differentiation in vivo as a potential strategy for oligodendroglial replacement and remyelination after spinal cord injury.
Supported by the Bavarian State Ministry of Sciences, Research and the Arts, “ForNeuroCell” grant.
