Article
Sustained functional benefit after transplantation of differentiated human neural stem cells following traumatic brain injury in the rat: a long-term neurofunctional and histochemical study
Anhaltender funktioneller Benefit nach Transplantation von differenzierten humanen neuralen Stammzellen nach experimentellem Schädel-Hirn-Trauma in der Ratte: eine funktionelle und histochemische Langzeitstudie
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Published: | April 11, 2007 |
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Objective: Traumatic brain injury (TBI) is inevitably associated with the loss of neural tissue. Till now there are no promising therapies to protect and repair neuronal loss after severe TBI and to improve neurological recovery. Due to the limited capacity for self repair, it seems logical to employ therapies which replace lost tissue in an appropriate organ-specific manner. Cellular strategies seem to be a promising approach.
This study investigates the effect of the transplantation (Tx) procedure in terms of the of cell application of human differentiated neural stem cells on the clinical outcome and the histomorphological changes after TBI in the rat.
Methods: Controlled Cortical Impact brain injury was employed in 72 male SD rats. Transplantation of either no cells, or a stereotactic intracerebral (~1x105 cells) or intravenous (~5x105 cells) transplantation of flourescence dye labeled differentiated neural stem cells was performed 24h after TBI. Evaluation of the neurological outcome by the rotarod-test, modified neurological severity score and beam-walk until 12 weeks after injury as well as histological characterisation of grafted cells and the effect on the penumbra zone.
Results: Brain injured animals, who received either intracerebral stereotactic or intravenous injection of flourescence labeled differerentiated human neural stem cells (dNSC), show cell migration into the penumbra zone of injury and survival of the graft. The transplanted groups demonstrate a long-lasting neurological improvement in all functional tests in comparison to the control group. Although we could detect the most grafted cells in the locally transplanted group, the systemically transplanted group shows the best performance being statistically significant better in comparison to the control group from day 8.
Conclusions: Our results demonstrate a sustained functional improvement of the neurological outcome following systemic and local transplantation of differentiated human stem cells after TBI. We could show migration and structural integration of the transplanted cells. Since systemic Tx demonstrates a higher therapeutic potency although more grafted cells could be detected after local Tx, neuroprotection seem to play a major role in our model.