title: Human umbilical cord blood stem cells upregulate matrix metalloproteinase-2 in rats after spinal cord injury.
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.
authors.affiliation: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA.
authors.forename: Krishna Kumar
authors.initials: KK
authors.lastname: Veeravalli
authors.forename: Venkata Ramesh
authors.initials: VR
authors.lastname: Dasari
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Tsung
authors.forename: Dzung H
authors.initials: DH
authors.lastname: Dinh
authors.forename: Meena
authors.initials: M
authors.lastname: Gujrati
authors.forename: Dan
authors.initials: D
authors.lastname: Fassett
authors.forename: Jasti S
authors.initials: JS
authors.lastname: Rao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002921:Cicatrix / Q000209:etiology / Q000601:surgery; D018920:Coculture Techniques / Q000379:methods; D036101:Cord Blood Stem Cell Transplantation; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000502:physiology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000601:surgery; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D007770:L-Lactate Dehydrogenase; D020778:Matrix Metalloproteinase 2