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

Veeravalli, Krishna Kumar; Dasari, Venkata Ramesh; Tsung, Andrew J.; Dinh, Dzung H.; Gujrati, Meena; Fassett, Daniel R.; Rao, Jasti S.

doi:10.1016/j.nbd.2009.07.012

Cited by 59 publications

(54 citation statements)

References 36 publications

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“…10 The forward and reverse primer sequences of rat MMP-12 used in this study have been reported earlier by our group. 15 Reaction set-up for each cDNA sample was assembled using the IQ SYBR Green Supermix kit (Bio-Rad Laboratories, CA) as per the manufacturer's instructions (see the online-only Data Supplement for further details).…”

Section: Quantitative Real-time Polymerase Chain Reactionmentioning

confidence: 99%

Matrix Metalloproteinase-12 Induces Blood–Brain Barrier Damage After Focal Cerebral Ischemia

Chelluboina

Klopfenstein

Pinson

et al. 2015

Stroke

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T he blood-brain barrier (BBB) is formed by the endothelial cells of cerebral microvessels, which are distinguished from peripheral endothelial cells by their lack of fenestrations, minimal pinocytotic activity, and the tight junctions (TJs).1 In addition to endothelial cells, the BBB is composed of pericytes, astrocytes, neurons, and extracellular matrix.2 Endothelial cells and pericytes are surrounded by the extracellular matrix, which is composed of structural proteins, such as collagen type-IV, laminin, fibronectin, elastin, thrombospondin, and various proteoglycans. The TJs between the endothelial cells of the cerebral microvessels serve to restrict blood-borne substances from entering the brain. The BBB thus provides a dynamic interface between the peripheral circulation and the brain.BBB disruption is an important contributing factor to brain injury that occurs after ischemic stroke. The expression of matrix metalloproteinases (MMPs) in the normal adult brain is very low or undetectable. In the injured brain, MMPs are expressed in various cell types, including resident and infiltrating inflammatory cells.3 However, the brain regions and cellular sources of expression differ for the specific MMPs, as well as the type, severity, and duration of injuries. 4 Ischemia leads to induction of MMPs, which contribute to BBB extracellular matrix degradation. The induction of these MMPs may further perpetuate BBB TJ permeability, thereby leading to BBB leakage, leukocyte infiltration, brain edema, and hemorrhage.2 MMP-2 and MMP-9 are considered the central mediators of ischemic BBB disruption because of their ability to degrade components of microvascular basal lamina, especially collagen type-IV, and to disrupt TJ proteins. [5][6][7][8] Recent investigations highlighted the possible pathological role for MMP-12 in the context of ischemic stroke. 9,10 MMP-12 is upregulated several fold higher than any other MMPs tested after focal cerebral ischemia, and its suppression attenuated the ischemic brain damage.10 Also, MMP-12 is reported to activate other MMPs, such as pro-MMP-2 and Background and Purpose-Matrix metalloproteinases (MMPs) have a central role in compromising the integrity of the blood-brain barrier (BBB). The role of MMP-12 in brain damage after ischemic stroke remains unknown. The main objective of the current study is to investigate the effect of MMP-12 suppression at an early time point before reperfusion on the BBB damage in rats. Methods-Sprague-Dawley rats were subjected to middle cerebral artery occlusion and reperfusion. MMP-12 shRNAexpressing plasmids formulated as nanoparticles were administered at a dose of 1 mg/kg body weight. The involvement of MMP-12 on BBB damage was assessed by performing various techniques, including Evans blue dye extravasation, 2,3,5-triphenyltetrazolium chloride staining, immunoblot, gelatin zymography, and immunofluorescence analysis. Results-MMP-12 is upregulated ≈31-, 47-, and 66-fold in rats subjected 1-, 2-, or 4-hour ischemia, respectively, followed by 1-day reperf...

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Section: Quantitative Real-time Polymerase Chain Reactionmentioning

confidence: 99%

Matrix Metalloproteinase-12 Induces Blood–Brain Barrier Damage After Focal Cerebral Ischemia

Chelluboina

Klopfenstein

Pinson

et al. 2015

Stroke

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“…Also, hUCBSC-induced upregulation of MMP-2 diminished the formation of the glial scar at the site of injury along with reduced immunoreactivity to chondroitin sulfate proteoglycans. This upregulation of MMP-2 levels and reduction of glial scar formation by hUCBSC treatment after SCI created an environment more favorable for endogenous repair mechanisms [77] (Figure 3). Kao et al [78] , suggested that hUCB derived-CD34 + cells can induce angiogenesis and endo/exogenous neurogenesis in SCI.…”

Section: Human Umbilical Cord Blood-derived Mscsmentioning

confidence: 99%

“…Upregulation of MMP2, reduction of glial scar hUCBSC treatment after SCI upregulates MMP-2 levels and reduces the formation of the glial scar Veeravalli et al [77] , 2009…”

Section: Downregulation Of Neuronal Apoptosismentioning

confidence: 99%

Mesenchymal stem cells in the treatment of spinal cord injuries: A review

Dasari

Veeravalli

Dinh

2014

WJSC

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With technological advances in basic research, the intricate mechanism of secondary delayed spinal cord injury (SCI) continues to unravel at a rapid pace. However, despite our deeper understanding of the molecular changes occurring after initial insult to the spinal cord, the cure for paralysis remains elusive. Current treatment of SCI is limited to early administration of high dose steroids to mitigate the harmful effect of cord edema that occurs after SCI and to reduce the cascade of secondary delayed SCI. R ecent evident-based clinical studies have cast doubt on the clinical benefit of steroids in SCI and intense focus on stem cell-based therapy has yielded some encouraging results. An array of mesenchymal stem cells (MSCs) from various sources with novel and promising strategies are being developed to improve function after SCI. In this review, we briefly discuss the pathophysiology of spinal cord injuries and characteristics and the potential sources of MSCs that can be used in the treatment of SCI. We will discuss the progress of MSCs application in research, focusing on the neuroprotective properties of MSCs. Finally, we will discuss the results from preclinical and clinical trials involving stem cell-based therapy in SCI. Core tip: Despite our deeper understanding of the molecular changes that occurs after the spinal cord injury (SCI), the cure for paralysis remains elusive. In this review, the pathophysiology of SCI and characteristics and potential sources of mesenchymal stem cells (MSCs) that can be used in the treatment of SCI were discussed. We also discussed the progress of application of MSCs in research focusing on the neuroprotective properties of MSCs. Finally, we discussed the results from preclinical and clinical trials involving stem cell-based therapy in SCI.

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“…Both the in vivo and in vitro studies support our hypothesis that the therapeutic mechanism of hUCBSC is inhibition of the neuronal apoptosis during the repair of injured spinal cord. Veeravalli et al (2009a) reported the involvement of tissue plasminogen activator (tPA) after SCI in rats and the role of hUCB stem cells. The tPA expression and activity were studied in vivo after SCI in rats and in vitro in rat embryonic spinal neurons in response to injury with staurosporine, hydrogen peroxide and glutamate.…”

Section: Wwwintechopencommentioning

confidence: 99%