| Abstract No.: | C-C3089 |
| Country: | Canada |
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| Title: | REHABILITATION ENHANCES RECOVERY FOLLOWING STEM CELL TRANSPLANTATION IN RODENT FOCAL ISCHEMIA |
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| Authors/Affiliations: | 1 Crystal MacLellan*; 1 Nichole Cumby; 1 Shirley Granter-Button; 1 Krista Hewlett; 1 Kathy McKay; 1 Garry Chernenko; 1 Dale Corbett;
1 Memorial University of Newfoundland, St. John's, NL, Canada
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| Content: | Objectives: The potential for using stem cells to treat a number of neurological disorders, including stroke, has garnered much interest, but the ability of stem cells to promote functional recovery must be rigorously assessed in animal models before transplantation studies progress to clinical trials. Our laboratory showed that enriched housing and exercise enhanced transplanted subventricular zone (SVZ) stem cell migration and improved functional benefit following stroke in rats, but that the majority of cells died within one month of transplantation. In the current study, we tested whether motor and cognitive rehabilitation augments stem cell transplantation after stroke.
Materials and Methods: Prior to surgery, 62 male Sprague Dawley rats were trained to reach for food reward pellets in the staircase task. Performance was also assessed in the horizontal ladder walking task, cylinder task, and elevated plus maze. Focal ischemia was induced by injecting the vasoconstrictive peptide endothelin-1 into the forelimb motor cortex and lateral striatum. Six days later, green fluorescent protein-expressing adult neural stem cells isolated from transgenic mouse SVZ (800 000 cells or vehicle) were injected into the ipsilateral sensory-motor cortex and striatum. Rats were then housed in the control (standard housing; 2 rats per cage) or enriched rehabilitation condition that consisted of living in an enriched environment (8 rats per large cage with various objects used to stimulate exploratory behaviour) plus motor (skilled reaching) and cognitive (Hebb-Williams maze) rehabilitation 6d/week. Functional recovery was assessed repeatedly over 2 months following transplantation, at which time rats were euthanized. Survival and migration of SVZ cells will be quantified using stereology. Transplanted cell phenotype will be identified with immunohistochemistry (e.g., NeuN, GFAP, NG-2 and DCX) and confocal microscopy.
Results: Preliminary analyses suggest that a significant proportion of stem cells survive out to 2 months and are located in the tissue surrounding the cortical injury and throughout the striatum. In the staircase task, rehabilitation and stem cells each provide modest functional improvement, but greatest recovery occurred with the combination of therapies. Further histological and behavioural analyses are ongoing.
Conclusion: Stroke survivors that receive stem cell transplantation may also receive and benefit from rehabilitation. Thus, it is important to examine how these therapies interact. Our results suggest that rehabilitation augments stem cell transplantation, possibly by enhancing neuronal plasticity required to support long-term stem cell survival. Future studies will explore the mechanisms of recovery and attempt to maximize efficacy of stem cell therapies for stroke.
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