Article
GLP-1 secreting encapsulated human mesenchymal stem cells for neuroprotection after traumatic brain injury in rats
GLP-1 sezernierende, gekapselte humane mesenchymale Stammzellen zur Neuroprotektion nach experimentellem Schädel-Hirn-Trauma
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Published: | April 11, 2007 |
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Objective: Neuroprotective treatment in the prevention of secondary injury after head trauma still lacks clinical applicability. In our experimental study of controlled cortical impact (CCI) in rats, we investigate, whether transplantation of Glucagon like Peptide-1 (GLP-1) -transfected stem cells encapsulated in alginate may prevent immunohistochemical cellular responses to brain injury.
Methods: CCI was applied to 50 Sprague-Dawley rats. Groups consisted of animals without treatment, animals with GLP-1-transfected human mesenchymal stem cells encapsulated in alginate beads, sham-treated animals with alginate capsules only, and sham-treated animals with encapsulated human stem cells without GLP-1-transfection. Alginate beads were stereotactically implanted into the right lateral ventricle before CCI. Seven untreated animals served as controls. 14 days post-injury, prior to sacrifice, GLP-1-concentrations in the CSF were measured. Anti-NeuN immunohistochemistry was used for assessment of vital hippocampal neurons in addition to glial Anti-GFAP and neuronal Anti-MAP2-immunostaining.
Results: Vital neurons were significantly decreased in the gyrus dentate hilus in the untreated and in both sham-treated animals when compared to controls and animals with GLP-1-transfected stem cells. Anti-GFAP and Anti-MAP2-immunohistochemistry assessed in the area of contusion mirrored the Anti-NeuN results, indicating less pronounced cellular reactive changes in the GLP-1 treated animals. Stem cells in the intraventricular compartment seem vital and GLP-1 peptide was observed at the trauma site.
Conclusions: Our immunohistological findings following treatment with GLP-1-transfected human mesenchymal stem cells in rats showed less cellular sequels after controlled cortical impact trauma. This may lead to new neurosurgical concepts for local neuroprotective therapy in acute brain injury.