GLP-1 secreting encapsulated human mesenchymal stem cells for neuroprotection
© Heile et al; licensee BioMed Central Ltd. 2007
Published: 20 December 2007
Neuroprotective treatment for the prevention of secondary injury to head injury still lacks clinical utility. In our experimental study of controlled cortical impact (CCI) in rats, we investigate, whether transplantation of GLP-1-transfected stem cells encapsulated in alginate may prevent cellular responses after trauma
Materials and methods
CCI was applied to 50 male adult Sprague-Dawley rats. Trauma groups consisted of trauma only, animals treated with GLP-1-transfected human mesenchymal stem cells (GLP-1 hMSC) encapsulated in alginate beads, with non-transfected encapsulated human mesenchymal stem cells (hMSC) and sham-treated with alginate capsules only (ALG). Seven healthy and untreated animals served as age-matched controls. Alginate beads were stereotactically implanted into the right lateral ventricle before CCI.14 days post-injury, GLP-1-concentrations in the CSF were measured and brains were histologically and immunohistochemically assessed using specific antibodies against NeuN, GFAP, MAP2 and GLP-1.
Anti-NeuN immunostaining showed a significant decrease of vital neurons in the dentate gyrus in the trauma animals as well as in the groups treated with non-transfected hMSC and with alginate capsules only. Both, GFAP and MAP2-immunohistochemistry, assessed in the area of contusion, mirrored the Anti-NeuN results showing less pronounced cellular reactive changes in the GLP-1 treated animals. Stem cells in the intraventricular compartment seem vital as well as positive staining of the GLP-1 peptide at the trauma site was observed.
Our immunohistological findings on treatment with GLP-1-transfected human mesenchymal stem cells in rats resulted in less histological sequels after controlled cortical impact trauma. This may break into new concepts for local neuroprotective therapy in traumatic brain injury as well as for other neurodegenerative diseases of the central nervous system, e.g. chronic hydrocephalus.
This article is published under license to BioMed Central Ltd.