Human umbilical cord blood stem cells upregulate matrix metalloproteinase-2 in rats after spinal cord injury

被引：99

作者：

Veeravalli, Krishna Kumar ^{[1
]}

Dasari, Venkata Ramesh ^{[1
]}

Tsung, Andrew J. ^{[2
]}

Dinh, Dzung H. ^{[2
]}

Gujrati, Meena ^{[3
]}

Fassett, Dan ^{[2
]}

Rao, Jasti S. ^{[1
,2
]}

机构：

[1] Univ Illinois, Dept Canc Biol & Pharmacol, Coll Med Peoria, Peoria, IL 61605 USA

[2] Univ Illinois, Dept Neurosurg, Coll Med Peoria, Peoria, IL 61605 USA

[3] Univ Illinois, Dept Pathol, Coll Med Peoria, Peoria, IL 61605 USA

来源：

NEUROBIOLOGY OF DISEASE | 2009年 / 36卷 / 01期

关键词：

Spinal cord injury; MMP-2; Human umbilical cord blood mesenchymal stem cells; Glial scar; Spinal neurons; CHONDROITIN-SULFATE PROTEOGLYCAN; BRAIN-BARRIER DISRUPTION; MYELIN BASIC-PROTEIN; FUNCTIONAL RECOVERY; MULTIPLE-SCLEROSIS; REACTIVE ASTROCYTES; CEREBROSPINAL-FLUID; CEREBRAL-ISCHEMIA; GELATINASE-B; EXPRESSION;

D O I：

10.1016/j.nbd.2009.07.012

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

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. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：200 / 212

页数：13

共 40 条

[1]

Pathogenesis and pharmacological strategies for mitigating secondary damage in acute spinal cord injury [J].

Amar, AP ;

Levy, ML .

NEUROSURGERY, 1999, 44 (05) :1027-1039

[2]

Matrix metalloproteinase expression in an experimentally-induced DTH model of multiple sclerosis in the rat CNS [J].

Anthony, DC ;

Miller, KM ;

Fearn, S ;

Townsend, MJ ;

Opdenakker, G ;

Wells, GMA ;

Clements, JM ;

Chandler, S ;

Gearing, AJH ;

Perry, VH .

JOURNAL OF NEUROIMMUNOLOGY, 1998, 87 (1-2) :62-72

[3]

Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia [J].

Asahi, M ;

Wang, XY ;

Mori, T ;

Sumii, T ;

Jung, JC ;

Moskowitz, MA ;

Fini, ME ;

Lo, EH .

JOURNAL OF NEUROSCIENCE, 2001, 21 (19) :7724-7732

[4]

Matrix metalloproteinases degrade myelin basic protein [J].

Chandler, S ;

Coates, R ;

Gearing, A ;

Lury, J ;

Wells, G ;

Bone, E .

NEUROSCIENCE LETTERS, 1995, 201 (03) :223-226

[5]

Chang C, 2001, TRENDS CELL BIOL, V11, pS37, DOI 10.1016/S0962-8924(01)82222-4

[6]

Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys [J].

Crowe, MJ ;

Bresnahan, JC ;

Shuman, SL ;

Masters, JN ;

Beattie, MS .

NATURE MEDICINE, 1997, 3 (01) :73-76

[7]

Umbilical cord blood stem cell mediated downregulation of Fas improves functional recovery of rats after spinal cord injury [J].

Dasari, Venkata Ramesh ;

Spomar, Daniel G. ;

Li, Liang ;

Gujrati, Meena ;

Rao, Jasti S. ;

Dinh, Dzung H. .

NEUROCHEMICAL RESEARCH, 2008, 33 (01) :134-149

[8]

Axonal remyelination by cord blood stem cells after spinal cord injury [J].

Dasari, Venkata Ramesh ;

Spomar, Daniel G. ;

Gondi, Christopher S. ;

Sloffer, Christopher A. ;

Saving, Kay L. ;

Gujrati, Meena ;

Rao, Jasti S. ;

Dinh, Dzung H. .

JOURNAL OF NEUROTRAUMA, 2007, 24 (02) :391-410

[9]

Duchossoy, Y ;

Horvat, JC ;

Stettler, O .

MOLECULAR AND CELLULAR NEUROSCIENCE, 2001, 17 (06) :945-956

[10]

Matrix metalloproteinase inhibition prevents oxidative stress-associated blood-brain barrier disruption after transient focal cerebral ischemia [J].

Gasche, Y ;

Copin, JC ;

Sugawara, T ;

Fujimura, M ;

Chan, PH .

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2001, 21 (12) :1393-1400

← 1 2 3 4 →