15-07-08(15:29:42)
Authors:
Christian Bernreuther(1,2)
Jinchong Xu(1)
Markus Glatzel(2)
Igor Jacovcevski(1)
Melitta Schachner(1)
Institutions:
1
Institut für die Biosynthese Neuraler Strukturen
Universitätsklinikum Hamburg-Eppendorf
Martinistrasse 52
20246 Hamburg
Germany
2
Institute of Neuropathology
University Medical Center Hamburg-Eppendorf
Martinistrasse 52
20246 Hamburg
Germany
Title of abstract : Transplanted neural stem cells expressing the neual cell adhesion molecule L1 under the influence of the promoter of the human glial fibrillary acidic protein enhance functional recovery in a mouse model of spinal cord injury.
Abstract text:
Functional recovery after spinal cord injury is an important goal in restorative medicine. Transplantation of genetically modified neural stem cells expressing favourable molecules to neutralize the inhibitory cues preventing regeneration in the central nervous system of mammals is a promising approach. In our study we have used green fluorescent protein-labeled murine neural stem cells that were derived from transgenic mice expressing the neural cell adhesion molecule L1 under the influence of the promoter of the human glial fibrillary acidic protein and transplanted these cells into the compression-lesioned spinal cord of mice. L1 is predominantly expressed by post-mitotic neurons in the CNS and by non-myelinating Schwann cells in the peripheral nervous system and plays an important role in the development and regeneration of the central nervous system. We found that in comparison to wild type control cells, neural stem cells overexpressing L1 showed enhanced differentiation into neurons and reduced differentiation into glial cells in vitro and generated more neurons and fewer astrocytes after transplantation into the lesioned spinal cord. Furthermore, lesioned animals grafted with L1 overexpressing neural stem cells showed enhanced soma size and synaptic coverage of host motoneurons. Behavioural analysis revealed enhanced functional recovery of lesioned mice grafted with L1 overexpressing neural stem cells when compared to wild type neural stem cells. These findings indicate that L1 overexpressing neural stem cells exert beneficial effects towards neuronal differentiation and can rescue host motoneurons enhancing functional recovery after transplantation into the lesioned spinal cord.
