Protective effects of MCI-186 on transplantation of bone marrow stromal cells in rat ischemic stroke model

Shen, Lihua; Ye, M.; Xin-sheng, Ding; Han, Qun; Zhang, C.; Liu, X.F.; Huang, Haoyue; Wu, Erbing; Gu, Xiaoyong

doi:10.1016/j.neuroscience.2012.08.001

Cited by 11 publications

(9 citation statements)

References 52 publications

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“…Previous studies found that enhancing endogenous antioxidant expression of cells could promote survival of these grafted cells. 25 26 27 28 Our finding that plasma levels of SOD and MDA were weakly to moderately correlated with circulating EPCs number at day 7 suggests that this antioxidant strategy might be valid in cell therapy at sub-acute stage of mild TBI.…”

Section: Discussionmentioning

confidence: 78%

“…The efficiency of cell therapy is determined by multiple factors, particularly the survival of donor cells in the hostile environment of a brain lesion. 25 Therefore, it is imperative to identify therapies that can protect donor cells in the host microenvironment. Antioxidant enzymes have been found to protect cells against the effects of oxidative stress of ROS after cerebral ischemia and reperfusion.…”

Section: Discussionmentioning

confidence: 99%

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Endothelial Progenitor Cells Correlated with Oxidative Stress after Mild Traumatic Brain Injury

et al. 2017

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PurposeEndothelial progenitor cells (EPCs) play a key role in tissue repair and regeneration. Previous studies have shown that infusion of human umbilical cord blood-derived endothelial colony-forming cells improves outcomes in mice subjected to experimental traumatic brain injury (TBI). However, the efficiency of cell transplantation is not satisfactory. Oxidative stress plays a significant role in the survival of transplanted cells following ischemic reperfusion injury. This observational clinical study investigated the correlation between the number of circulating EPCs and plasma levels of superoxide dismutase (SOD) and malonyldialdehyde (MDA).Materials and MethodsPeripheral blood samples were collected from 20 patients with mild TBI at day-1, day-2, day-3, day-4, and day-7 post TBI. The number of circulating EPCs and the plasma levels of SOD and MDA were measured.ResultsThe average of circulating EPCs in TBI patients decreased initially, but increased thereafter, compared with healthy controls. Plasma levels of SOD in TBI patients were significantly lower than those in healthy controls at day-4 post-TBI. MDA levels showed no difference between the two groups. Furthermore, when assessed on day-7 post-TBI, the circulating EPC number were correlated with the plasma levels of SOD and MDA.ConclusionThese results suggest that the number of circulating EPCs is weakly to moderately correlated with plasma levels of SOD and MDA at day-7 post-TBI, which may offer a novel antioxidant strategy for EPCs transplantation after TBI.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Endothelial Progenitor Cells Correlated with Oxidative Stress after Mild Traumatic Brain Injury

et al. 2017

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“…[ 23 ] Both human and animal experiments revealed that MCI-186 could protect NSCs from irradiation and increase their proliferation around the brain lesion. [ 24 25 26 ] In the previous study, we also observed that MCI-186 significantly reduced the consumption of antioxidase superoxide dismutase and the oxidative product of malondialdehyde,[ 27 ] the mechanism of its improving SDF-1 expression needs further explore.…”

Section: Discussionmentioning

confidence: 99%

Possible Mechanism of Therapeutic Effect of 3-Methyl-1-phenyl-2-pyrazolin-5-one and Bone Marrow Stromal Cells Combination Treatment in Rat Ischemic Stroke Model

Shen

Jin

Shen

et al. 2016

Chinese Medical Journal

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Background:The functional improvement following bone marrow stromal cells (BMSCs) transplantation after stroke is directly related to the number of engrafted cells and neurogenesis in the injured brain. Here, we tried to evaluate whether 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), a free radical scavenger, might influence BMSCs migration to ischemic brain, which could promote neurogenesis and thereby enhance treatment effects after stroke.Methods:Rat transient middle cerebral artery occlusion (MCAO) model was established. Two separate MCAO groups were administered with either MCI-186 or phosphate-buffered saline (PBS) solution to evaluate the expression of stromal cell-derived factor-1 (SDF-1) in ischemic brain, and compared to that in sham group (n = 5/group/time point[at 1, 3, and 7 days after operation]). The content of chemokine receptor-4 (CXCR4, a main receptor of SDF-1) at 7 days after operation was also observed on cultured BMSCs. Another four MCAO groups were intravenously administered with either PBS, MCI-186, BMSCs (2 × 106), or a combination of MCI-186 and BMSCs (n = 10/group). 5-bromo-2-deoxyuridine (BrdU) and Nestin double-immunofluorescence staining was performed to identify the engrafted BMSCs and neuronal differentiation. Adhesive-removal test and foot-fault evaluation were used to test the neurological outcome.Results:MCI-186 upregulated the expression of SDF-1 in ischemic brain and CXCR4 content in BMSCs was enhanced after hypoxic stimulation. When MCAO rats were treated with either MCI-186, BMSCs, or a combination of MCI-186 and BMSCs, the neurologic function was obviously recovered as compared to PBS control group (P < 0.01 or 0.05, respectively). Combination therapy represented a further restoration, increased the number of BMSCs and Nestin+ cells in ischemic brain as compared with BMSCs monotherapy (P < 0.01). The number of engrafted-BMSCs was correlated with the density of neuronal cells in ischemic brain (r = 0.72, P < 0.01) and the improvement of foot-fault (r = 0.70, P < 0.01).Conclusion:MCI-186 might promote BMSCs migration to the ischemic brain, amplify the neurogenesis, and improve the effects of cell therapy.

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“…Two investigators (Y.W. and S.G.) independently examined reference lists manually from included original studies, 19–59 as well as review articles. 14–17…”

Section: Methodsmentioning

confidence: 99%

Bone marrow stromal cell therapy for ischemic stroke: A meta-analysis of randomized control animal trials

Wang

Demaerschalk

et al. 2016

International Journal of Stroke

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Background Results of animal studies assessing efficacy of bone marrow stromal cell therapy for ischemic stroke remain inconsistent. Aims The aims are to assess efficacy of bone marrow stromal cell therapy for ischemic stroke in animal studies. Methods Randomized controlled animal trials assessing efficacy of bone marrow stromal cell therapy were eligible. Stroke therapy academic industry round table was used to assess methodologic quality of included studies. Primary outcomes were total infarction volume and modified Neurological Severity Score. Multiple prespecified sensitivity analyses and subgroup analyses were conducted. Random effects models were used for meta-analysis. Results Thirty-three randomized animal trials were included with a total of 796 animals. The median quality score was 6 (interquartile range, 5-7). Bone marrow stromal cell therapy decreased total infarction volume (standardized mean difference, 0.897; 95% confidence interval, 0.553-1.241; P < .001) at follow-up. Overall standardized mean difference between animals treated with bone marrow stromal cell and controls was 2.47 (95% confidence interval, 1.84-3.11; P < .001) for modified Neurological Severity Score; 1.27 (95% confidence interval, 0.72-1.82; P < .001) for adhesive removal test; and 2.13 (95% confidence interval, 0.65-3.61; P < .001) for rotarod test. Significant heterogeneity among studies was observed. Effect of all outcomes stayed significant in various sensitivity analyses and subgroup analyses, except in a few subgroup analyses with small sample size or with short time follow-up. No significant difference between groups was observed except for study location, in which significantly larger estimates were found in Asian countries. On the basis of this meta-analysis, larger sample sizes are warranted for future animal studies. Conclusions Bone marrow stromal cell therapy significantly decreased total infarction volume and increased neural functional recovery in randomized controlled animal models of ischemic stroke.

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Protective effects of MCI-186 on transplantation of bone marrow stromal cells in rat ischemic stroke model

Cited by 11 publications

References 52 publications

Endothelial Progenitor Cells Correlated with Oxidative Stress after Mild Traumatic Brain Injury

Endothelial Progenitor Cells Correlated with Oxidative Stress after Mild Traumatic Brain Injury

Possible Mechanism of Therapeutic Effect of 3-Methyl-1-phenyl-2-pyrazolin-5-one and Bone Marrow Stromal Cells Combination Treatment in Rat Ischemic Stroke Model

Bone marrow stromal cell therapy for ischemic stroke: A meta-analysis of randomized control animal trials

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