title: Seven days post-injury fate and effects of genetically labelled adipose-derived mesenchymal cells on a rat traumatic brain injury experimental model.
abstract: Mesenchymal stromal cells (MSC) have been suggested to have beneficial effects on animal models of traumatic brain injury (TBI), owing to their neurotrophic and immunomodulatory properties. Adipose tissue-derived stromal cells (ASCs) are multipotent MSC that can be harvested with minimally invasive methods, show a high proliferative capacity, low immunogenicity if allogeneic, and can be used in autologous or heterologous settings. In the present study ASCs were genetically labelled using the Sleeping Beauty transposon to express the fluorescent protein Venus. Venus+ASCs were transplanted intra-cerebroventricularly (ICV), on a rat TBI model and their survival, fate and effects on host brain responses were examined at seven days post-injury (7dPI). We provide evidence that Venus+ASCs survived, migrated into the periventricular striatum and were negative for neuronal or glial lineage differentiation markers. Venus+ASCs stimulated the proliferation of endogenous neural stem cells (NSCs) in the brain neurogenic niches, the subventricular zone (SVZ) and the hippocampal dentate gyrus (DG). It was also evident that Venus+ASCs modify the host brain's cellular microenvironment both at the injury site and at their localization area by promoting a significant reduction of the lesion area, as well as altering the post-injury, pro-inflammatory profile of microglial and astrocytic cell populations. Our data support the view that ICV transplantation of ASCs induces alterations in the host brain's cellular response to injury that may be correlated to a reversal from a detrimental to a beneficial state which is permissive for regeneration and repair.
authors.affiliation: Laboratory of Anatomy, Histology and Embryology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Dori
authors.affiliation: Biohellenika, Pylaia, Thessaloniki, Greece.
authors.forename: Spyros
authors.initials: S
authors.lastname: Petrakis
authors.affiliation: Laboratory of Anatomy, Histology and Embryology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Giannakopoulou
authors.affiliation: Laboratory of Anatomy, Histology and Embryology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Chryssa
authors.initials: C
authors.lastname: Bekiari
authors.affiliation: Laboratory of Anatomy, Histology and Embryology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Grivas
authors.affiliation: Biohellenika, Pylaia, Thessaloniki, Greece.
authors.forename: Evangelia K
authors.initials: EK
authors.lastname: Siska
authors.affiliation: Biohellenika, Pylaia, Thessaloniki, Greece.|Department of Biochemistry, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki,, Thessaloniki, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Koliakos
authors.affiliation: Laboratory of Anatomy, Histology and Embryology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece. gpapadop@vet.auth.gr.
authors.forename: Georgios C
authors.initials: GC
authors.lastname: Papadopoulos
mesh_terms: D017667:Adipocytes / Q000502:physiology* / Q000637:transplantation*; D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000473:pathology / Q000628:therapy*; D002454:Cell Differentiation; D049109:Cell Proliferation; D060833:Cellular Microenvironment; D002540:Cerebral Cortex / Q000293:injuries / Q000473:pathology; D005434:Flow Cytometry; D057967:Infusions, Intraventricular; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D058953:Neural Stem Cells; D055495:Neurogenesis; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome