Human umbilical cord blood stem cells upregulate matrix metalloproteinase-2 in rats after spinal cord injury.
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.
Veeravalli
Krishna Kumar
KK
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA.
Dasari
Venkata Ramesh
VR
Tsung
Andrew J
AJ
Dinh
Dzung H
DH
Gujrati
Meena
M
Fassett
Dan
D
Rao
Jasti S
JS
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*
D019714:Tissue Inhibitor of Metalloproteinases; D007770:L-Lactate Dehydrogenase; D020778:Matrix Metalloproteinase 2