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Human umbilical cord blood stem cells upregulate matrix metalloproteinase-2 in rats after spinal cord injury
Authors:Krishna Kumar Veeravalli  Venkata Ramesh Dasari  Andrew J Tsung  Dzung H Dinh  Meena Gujrati  Dan Fassett  Jasti S Rao  
Institution:aDepartment of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA;bDepartment of Neurosurgery, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA;cDepartment of Pathology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
Abstract:Matrix metalloproteinases (MMPs) are a large family of proteolytic enzymes involved in inflammation, wound healing and other pathological processes after neurological disorders. MMP-2 promotes functional recovery after spinal cord injury (SCI) by regulating the formation of a glial scar. In the present study, we aimed to investigate the expression and/or activity of several MMPs, after SCI and human umbilical cord blood mesenchymal stem cell (hUCB) treatment in rats with a special emphasis on MMP-2. Treatment with hUCB after SCI altered the expression of several MMPs in rats. MMP-2 is upregulated after hUCB treatment in spinal cord injured rats and in spinal neurons injured either with staurosporine or hydrogen peroxide. Further, hUCB induced upregulation of MMP-2 reduced formation of the glial scar at the site of injury along with reduced immunoreactivity to chondroitin sulfate proteoglycans. Blockade of MMP-2 activity in hUCB cocultured injured spinal neurons reduced the protection offered by hUCB which indicated the involvement of MMP-2 in the neuroprotection offered by hUCB. Based on these results, we conclude that hUCB treatment after SCI upregulates MMP-2 levels and reduces the formation of the glial scar thereby creating an environment suitable for endogenous repair mechanisms.
Keywords:Spinal cord injury  MMP-2  Human umbilical cord blood mesenchymal stem cells  Glial scar  Spinal neurons
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