Stem cell transplantation for ischemic stroke.
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ABSTRACT:
SUBMITTER: Boncoraglio GB
PROVIDER: S-EPMC6500737 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Brain ischemic stroke is one of the most common causes of death and disability, currently has no efficient therapeutic strategy in clinic. Due to irreversible functional neurons loss and neural tissue injury, stem cell transplantation may be the most promising treatment approach. Neural stem cells (NSCs) as the special type of stem cells only exist in the nervous system, can differentiate into neurons, astrocytes, and oligodendrocytes, and have the abilities to compensate insufficient endogenous nerve cells and improve the inflammatory microenvironment of cell survival. In this review, we focused on the important role of NSCs therapy for brain ischemic stroke, mainly introduced the methods of optimizing the therapeutic efficacy of NSC transplantation, such as transfection and overexpression of specific genes, pretreatment of NSCs with inflammatory factors, and co-transplantation with cytokines. Next, we discussed the potential problems of NSC transplantation which seriously limited their rapid clinical transformation and application. Finally, we expected a new research topic in the field of stem cell research. Based on the bystander effect, exosomes derived from NSCs can overcome many of the risks and difficulties associated with cell therapy. Thus, as natural seed resource of nervous system, NSCs-based cell-free treatment is a newly therapy strategy, will play more important role in treating ischemic stroke in the future.
| S-EPMC6828598 | biostudies-literature
Project description:IntroductionCell-based therapy is considered as promising strategy to cure stroke. However, employing appropriate type of stem cell to fulfill many therapeutic needs of cerebral ischemia is still challenging. In this regard, the current study was designed to elucidate therapeutic potential of epidermal neural crest stem cells (EPI-NCSCs) compared to bone marrow mesenchymal stem cells (BM-MSCs) in rat model of ischemic stroke.MethodsIschemic stroke was induced by middle cerebral artery occlusion (MCAO) for 45 minutes. Immediately after reperfusion, EPI-NCSCs or BM-MSCs were transplanted via intra-arterial or intravenous route. A test for neurological function was performed before ischemia and 1, 3, and 7 days after MCAO. Also, infarct volume ratio and relative expression of 15 selected target genes were evaluated 7 days after transplantation.ResultsEPI-NCSCs transplantation (both intra-arterial and intravenous) and BM-MSCs transplantation (only intra-arterial) tended to result in a better functional outcome, compared to the MCAO group; however, this difference was not statistically significant. The infarct volume ratio significantly decreased in NCSC-intra-arterial, NCSC-intravenous and MSC-intra-arterial groups compared to the control. EPI-NCSCs interventions led to higher expression levels of Bdnf, nestin, Sox10, doublecortin, β-III tubulin, Gfap, and interleukin-6, whereas neurotrophin-3 and interleukin-10 were decreased. On the other hand, BM-MSCs therapy resulted in upregulation of Gdnf, β-III tubulin, and Gfap and down-regulation of neurotrophin-3, interleukin-1, and interleukin-10.ConclusionThese findings highlight the therapeutic effects of EPI-NCSCs transplantation, probably through simultaneous induction of neuronal and glial formation, as well as Bdnf over-expression in a rat model of ischemic stroke.
| S-EPMC7298983 | biostudies-literature
Project description:Intraparenchymal transplantation of neural stem/progenitor cells (NSPCs) has been extensively investigated in animal models of ischemic stroke. However, the reported therapeutic efficacy was inconsistent among studies. To evaluate this situation, PubMed, Embase, and Web of Science databases were searched for preclinical studies using NSPC intraparenchymal transplantation in ischemic stroke animals. Data of study quality score, neurobehavioral (mNSS, rotarod test, and cylinder test) and histological (infarct volume) outcomes, cell therapy-related serious adverse events, and related cellular mechanisms were extracted for meta-analysis and systematic review. A total of 62 studies containing 73 treatment arms were included according to our criterion, with a mean quality score of 5.10 in 10. Among these studies, almost half of the studies claimed no adverse events of tumorigenesis. The finally pooled effect sizes for neurobehavioral and histological assessments were large (1.27 for mNSS, 1.63 for the rotarod test, 0.71 for the cylinder test, and 1.11 for infarct volume reduction). With further analysis, it was found that the administration time poststroke, NSPC donor species, and transplantation immunogenicity had close correlations with the degree of infarct volume reduction. The NSPC dosage delivered into the brain parenchyma was also negatively correlated with the effect of the cylinder test. Intriguingly, endogenous apoptosis inhibition and axonal regeneration played the most critical role in intraparenchymal NSPC transplantation among the cellular mechanisms. These results indicate that intraparenchymal NSPC transplantation is beneficial for neurobehavioral and histological improvement and is relatively safe for ischemic stroke animals. Therefore, intraparenchymal NSPC transplantation is a promising treatment for stroke patients.
| S-EPMC6189667 | biostudies-literature
Project description:Accumulating preclinical evidence suggests the use of amnion as a source of stem cells for investigations of basic science concepts related to developmental cell biology, but also for stem cells' therapeutic applications in treating human disorders. We previously reported isolation of viable rat amniotic fluid-derived stem (AFS) cells. Subsequently, we recently reported the therapeutic benefits of intravenous transplantation of AFS cells in a rodent model of ischemic stroke. Parallel lines of investigations have provided safety and efficacy of stem cell therapy for treating stroke and other neurological disorders. This review article highlights the need for investigations of mechanisms underlying AFS cells' therapeutic benefits and discusses lab-to-clinic translational gating items in an effort to optimize the clinical application of the cell transplantation for stroke.
| S-EPMC4131212 | biostudies-other
Project description:The regenerative potential of brain has led to emerging therapies that can cure clinico-motor deficits after neurological diseases. Bone marrow mononuclear cell therapy is a great hope to mankind as these cells are feasible, multipotent and aid in neurofunctional gains in Stroke patients.This study evaluates safety, feasibility and efficacy of autologous mononuclear (MNC) stem cell transplantation in patients with chronic ischemic stroke (CIS) using clinical scores and functional imaging (fMRI and DTI).Non randomised controlled observational study Study: Twenty four (n=24) CIS patients were recruited with the inclusion criteria as: 3 months-2years of stroke onset, hand muscle power (MRC grade) at least 2; Brunnstrom stage of recovery: II-IV; NIHSS of 4-15, comprehendible. Fugl Meyer, modified Barthel Index (mBI) and functional imaging parameters were used for assessment at baseline, 8 weeks and at 24 weeks. Twelve patients were administered with mean 54.6 million cells intravenously followed by 8 weeks of physiotherapy. Twelve patients served as controls. All patients were followed up at 24 weeks.The laboratory and radiological outcome measures were within normal limits in MNC group. Only mBI showed statistically significant improvement at 24 weeks (p<0.05) whereas the mean FM, MRC, Ashworth tone scores in the MNC group were high as compared to control group. There was an increased number of cluster activation of Brodmann areas BA 4, BA 6 post stem cell infusion compared to controls indicating neural plasticity. Cell therapy is safe and feasible which may facilitate restoration of function in CIS.
| S-EPMC3908296 | biostudies-other
Project description:Stroke is the leading cause of serious long-term disability, significantly reducing mobility in almost half of the affected patients aged 65 years and older. There are currently no proven neurorestorative treatments for chronic stroke. To address the complex problem of restoring function in ischemic brain tissue, stem cell transplantation-based therapies have emerged as potential restorative therapies. Aligning with the major cell types found within the ischemic brain, stem-cell-based clinical trials for ischemic stroke have fallen under three broad cell lineages: hematopoietic, mesenchymal, and neural. In this review article, we will discuss the scientific rationale for transplanting cells from each of these lineages and provide an overview of published and ongoing trials using this framework.
| S-EPMC7767918 | biostudies-literature
Project description:AIMS:Intravenous transplantation of bone marrow mesenchymal stem cells (BMSCs) had been documented to improve functional outcome after ischemic stroke. However, the timing and appropriate cell number of transplantation to achieve better outcome after an episode of stroke remain further to be optimized. METHODS:To determine the optimal conditions, we transplanted different concentrations of BMSCs at different time points in a rat model of ischemic stroke. Infarction volume and neurological behavioral tests were performed after ischemia. RESULTS:We found that transplantation of BMSCs at 3 and 24 h, but not 7 days after focal ischemia, significantly reduced the lesion volume and improved motor deficits. We also found that transplanted cells at 1 × 10(6) to 10(7) , but not at 1 × 10(4) to 10(5) , significantly improved functional outcome after stroke. In addition to inhibiting macrophages/microglia activation in the ischemic brain, BMSC transplantation profoundly reduced infiltration of gamma delta T (??T) cells, which are detrimental to the ischemic brain, and significantly increased regulatory T cells (Tregs), along with altered Treg-associated cytokines in the ischemic brain. CONCLUSIONS:Our data suggest that timing and cell dose of transplantation determine the therapeutic effects after focal ischemia by modulating poststroke neuroinflammation.
| S-EPMC6493061 | biostudies-literature
Project description:Transplantation of neural stem cells (NSCs) is a promising therapy for ischemic stroke. However, the effectiveness of this approach is limited by grafted cell death. Breast cancer susceptibility protein 1 (BRCA1) could suppress apoptosis in neural progenitors and modulate oxidative stress in neurons. In this study, we found that BRCA1 was upregulated by oxygen-glucose deprivation/reoxygenation (OGD/R). Overexpression of BRCA1 in NSCs reduced cell apoptosis and oxidative stress after OGD/R insult. The molecule overexpression also stimulated cellular proliferation in OGD/R NSCs and increased the survival rate of grafted cells. Further, the transplantation of BRCA1-transfected NSCs into mice with ischemic stroke increased brain-derived neurotropic factor and nerve growth factor expression in the brain and elicited neurological function improvement. In addition, we found that RING finger domain and BRCT domain of BRCA1 could physically interact with p53 in NSCs. The cross talk between BRCA1 RING finger domain and p53 was responsible for p53 ubiquitination and degradation. Our findings indicate that modification with BRCA1 could enhance the efficacy of NSCs transplantation in ischemic stroke.
| S-EPMC6470423 | biostudies-literature
Project description:ObjectiveThe aim of this study was to evaluate the efficacy and safety of the mesenchymal stem cell (MSC) therapy in patients with ischemic stroke (IS).Materials and methodsClinical trials involved in this research were searched from PubMed, Web of Science, Cochrane Library, Embase, Wanfang and CNKI database. Therapeutic effects of MSC therapy were assessed according to National Institutes of Health Stroke Scale (NIHSS), Barthel index (BI), Fugl-Meyer Assessment (FMA) and Functional Independence Measure (FIM), and its safety was evaluated based on adverse events.ResultsThis research covered 23 trials including 1,279 IS patients. Based on our analysis, the overall condition of IS patients significantly improved after MSC therapy, indicated by decreased NIHSS and increased BI, FMA and FIM scores. Our analysis also showed that the treatment effects in the MSC transplantation group were superior to those in the control group (routine medication therapy) with statistical significance for NIHSS (1 month after therapy: odds ratio [OR]=-1.92, CI=-3.49 to -0.34, P=0.02; 3 months after therapy: OR=-2.65, CI=-3.40 to -1.90, P<0.00001), BI (1 month after therapy: OR=0.99, CI=0.19-1.79, P=0.02; 6 months after therapy: OR=10.10, CI=3.07-17.14, P=0.005), FMA (3 months after therapy: OR=10.20, CI=3.70-16.70, P=0.002; 6 months after therapy: OR=10.82, CI=6.45-15.18, P<0.00001) and FIM (1 month after therapy: OR=15.61, CI=-0.02 to 31.24, P=0.05; 6 months after therapy: OR=16.56, CI=9.06-24.06, P<0.0001). No serious adverse events were reported during MSC therapy.ConclusionMSC therapy is safe and effective in treating IS by improving the neurological deficits, motor function and daily life quality of patients.
| S-EPMC5957058 | biostudies-literature
Project description:Despite recent developments in innovative treatment strategies, stroke remains one of the leading causes of death and disability worldwide. Stem cell therapy is currently attracting much attention due to its potential for exerting significant therapeutic effects on stroke patients. Various types of cells, including bone marrow mononuclear cells, bone marrow/adipose-derived stem/stromal cells, umbilical cord blood cells, neural stem cells, and olfactory ensheathing cells have enhanced neurological outcomes in animal stroke models. These stem cells have also been tested via clinical trials involving stroke patients. In this article, the authors review potential molecular mechanisms underlying neural recovery associated with stem cell treatment, as well as recent advances in stem cell therapy, with particular reference to clinical trials and future prospects for such therapy in treating stroke.
| S-EPMC7582939 | biostudies-literature