The Efficacy of Mesenchymal Stem Cell Therapies in Rodent Models of Multiple Sclerosis: An Updated Systematic Review and Meta-Analysis
Ontology highlight
ABSTRACT:
SUBMITTER: He J
PROVIDER: S-EPMC8427822 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundMesenchymal stem cells (MSCs) and MSCs-derived extracellular vesicles (EVs) have emerged as potential novel therapies for subarachnoid hemorrhage (SAH). However, their effects remain incompletely understood. We aim to comprehensively evaluate the effect of MSCs-derived therapies in rodent models of SAH.MethodsWe searched PubMed, EMBASE, and Web of Science up to September 2021 to identify studies that reported the effects of MSCs or MSCs-derived EVs in a rodent SAH model. Neurobehavioral score was extracted as the functional outcome, and brain water content was measured as the histopathological outcome. A random-effects model was used to calculate the standardized mean difference (SMD) and confidence interval (CI).ResultsNine studies published from 2018 to 2021 met the inclusion criteria. Studies quality scores ranged from 5 to 10, with a mean value of 7.22. Our results revealed an overall positive effect of MSCs and MSCs-derived EVs on the neurobehavioral score with a SMD of - 2.21 (95% CI - 3.14, - 1.08; p < 0.0001). Meanwhile, we also found that MSCs and MSCs-derived EVs reduced brain water content by a SMD of - 2.09 (95% CI - 2.99, - 1.19; p < 0.00001). Significant heterogeneity among studies was observed, further stratified and sensitivity analyses did not identify the source of heterogeneity.ConclusionsOur results suggested that MSCs-derived therapies prominently improved functional recovery and reduced brain edema in the rodent models of SAH. Notably, the limitations of small sample size should be considered when interpreting the results, and large animal studies and human trials are needed for further investigation.
| S-EPMC8800223 | biostudies-literature
Project description:BackgroundMultiple preclinical studies have demonstrated that bone-marrow derived mesenchymal stromal (stem) cells [MSC(M)] positively influence the severity of sepsis symptoms and mortality in rodent models. However, this remains an inconclusive finding.ObjectiveTo review the effect of naïve MSC(M) in rodent models of sepsis.MethodsThe PubMed, EMBASE, and Web of Science databases were searched up to August 31, 2021. Inclusion criteria according to PICOS criteria were as follows: (1) population: rodents; (2) intervention: unmodified MSC(M); (3) comparison: not specified; (4) primary outcome: the effects of MSC(M) cell therapy on the mortality of rodent models of sepsis and endotoxemia; (5) study: experimental studies. Multiple prespecified subgroup and meta-regression analysis were conducted. Following quality assessment, random effects models were used for this meta-analysis.The inverse variance method of the fixed effects model was used to calculate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs).Resultstwenty-four animal studies met the inclusion criteria. Our results revealed an overall OR difference between animals treated with naïve MSC(M) and controls for mortality rate was 0.34(95% confidence interval: 0.27-0.44; P < 0.0001). Significant heterogeneity among studies was observed.ConclusionsThe findings of this meta-analysis suggest that naïve MSC(M) therapy decreased mortality in rodent models of sepsis. Additionally, we identified several key knowledge gaps, including the lack of large animal studies and uncertainty regarding the optimal dose of MSC(M) transplantation in sepsis. Before MSC(M) treatment can advance to clinical trials, these knowledge gaps must be addressed.
| S-EPMC8761857 | biostudies-literature
Project description:Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination and axonal degeneration. MS patients typically present with a relapsing-remitting (RR) disease course, manifesting as sporadic attacks of neurological symptoms including ataxia, fatigue, and sensory impairment. While there are several effective disease-modifying therapies able to address the inflammatory relapses associated with RRMS, most patients will inevitably advance to a progressive disease course marked by a gradual and irreversible accrual of disabilities. Therapeutic intervention in progressive MS (PMS) suffers from a lack of well-characterized biological targets and, hence, a dearth of successful drugs. The few medications approved for the treatment of PMS are typically limited in their efficacy to active forms of the disease, have little impact on slowing degeneration, and fail to promote repair. In looking to address these unmet needs, the multifactorial therapeutic benefits of stem cell therapies are particularly compelling. Ostensibly providing neurotrophic support, immunomodulation and cell replacement, stem cell transplantation holds substantial promise in combatting the complex pathology of chronic neuroinflammation. Herein, we explore the current state of preclinical and clinical evidence supporting the use of stem cells in treating PMS and we discuss prospective hurdles impeding their translation into revolutionary regenerative medicines.
| S-EPMC8299560 | biostudies-literature
Project description:BackgroundMultiple sclerosis (MS) is a leading cause of disability in young adults. Susceptibility to MS is determined by environmental exposure on the background of genetic risk factors. A previous meta-analysis suggested that smoking was an important risk factor for MS but many other studies have been published since then.Methods/principal findingsWe performed a Medline search to identify articles published that investigated MS risk following cigarette smoking. A total of 14 articles were included in this study. This represented data on 3,052 cases and 457,619 controls. We analysed these studies in both a conservative (limiting our analysis to only those where smoking behaviour was described prior to disease onset) and non-conservative manner. Our results show that smoking is associated with MS susceptibility (conservative: risk ratio (RR) 1.48, 95% confidence interval (CI) 1.35-1.63, p < 10⁻¹⁵; non-conservative: RR 1.52, 95% CI 1.39-1.66, p < 10⁻¹⁹). We also analysed 4 studies reporting risk of secondary progression in MS and found that this fell just short of statistical significance with considerable heterogeneity (RR 1.88, 95% CI 0.98-3.61, p = 0.06).DiscussionOur results demonstrate that cigarette smoking is important in determining MS susceptibility but the effect on the progression of disease is less certain. Further work is needed to understand the mechanism behind this association and how smoking integrates with other established risk factors.
| S-EPMC3020969 | biostudies-literature
Project description:An unmet but urgent medical need is the development of myelin repair promoting therapies for Multiple Sclerosis (MS). Many such therapies have been pre-clinically tested using different models of toxic demyelination such as cuprizone, ethidium bromide, or lysolecithin and some of the therapies already entered clinical trials. However, keeping track on all these possible new therapies and their efficacy has become difficult with the increasing number of studies. In this study, we aimed at summarizing the current evidence on such therapies through a systematic review and at providing an estimate of the effects of tested interventions by a meta-analysis. We show that 88 different therapies have been pre-clinically tested for remyelination. 25 of them (28%) entered clinical trials. Our meta-analysis also identifies 16 promising therapies which did not enter a clinical trial for MS so far, among them Pigment epithelium-derived factor, Plateled derived growth factor, and Tocopherol derivate TFA-12.We also show that failure in bench to bedside translation from certain therapies may in part be attributable to poor study quality. By addressing these problems, clinical translation might be smoother and possibly animal numbers could be reduced.
| S-EPMC6351564 | biostudies-literature
Project description:Mesenchymal stem cells (MSCs) have emerged as a potential therapy for a range of neural insults. In animal models of multiple sclerosis, an autoimmune disease that targets oligodendrocytes and myelin, treatment with human MSCs results in functional improvement that reflects both modulation of the immune response and myelin repair. Here we demonstrate that conditioned medium from human MSCs (MSC-CM) reduces functional deficits in mouse MOG35–55-induced experimental autoimmune encephalomyelitis (EAE) and promotes the development of oligodendrocytes and neurons. Functional assays identified hepatocyte growth factor (HGF) and its primary receptor cMet as critical in MSC-stimulated recovery in EAE, neural cell development and remyelination. Active MSC-CM contained HGF, and exogenously supplied HGF promoted recovery in EAE, whereas cMet and antibodies to HGF blocked the functional recovery mediated by HGF and MSC-CM. Systemic treatment with HGF markedly accelerated remyelination in lysolecithin-induced rat dorsal spinal cord lesions and in slice cultures. Together these data strongly implicate HGF in mediating MSC-stimulated functional recovery in animal models of multiple sclerosis.
| S-EPMC3427471 | biostudies-literature
Project description:The assurance of safety and effectiveness is a significant focal point in all therapeutic approaches. Although mesenchymal stem cells (MSCs) have been identified as a potential novel therapeutic strategy for multiple sclerosis (MS), existing evidence regarding the effectiveness and safety of this strategy remains inconclusive. Thus, the primary aim of this systematic review and meta-analysis (SRMA) was to comprehensively assess the effectiveness and safety of MSC therapy in individuals diagnosed with MS. A comprehensive search was conducted using appropriate keywords in the PubMed, Scopus, Cochrane, ScienceDirect, and Google Scholar databases to determine the eligible studies. The change in the expanded disability status scale (EDSS) score from baseline to follow-up was used to assess MSC efficacy. The effectiveness of the therapy was assessed using a random-effects model, which calculated the combined prevalence and 95% confidence intervals (CIs) for MS patients who experienced improvement, stability, or worsening of their condition. The protocol was registered in PROSPERO (CRD42020209671). The findings indicate that 40.4% (95% CI: 30.6-50.2) of MS patients exhibited improvements following MSC therapy, 32.8% (95% CI: 25.5-40.1) remained stable, and 18.1% (95% CI: 12.0-24.2) experienced a worsening of their condition. Although no major complications were observed, headaches 57.6 [37.9-77.3] and fever 53.1 [20.7-85.4] were commonly reported as minor adverse events. All of the results reported in this meta-analysis are consistent and credible according to the sensitivity analyses. Regardless of different individual studies, our meta-analysis provides a comprehensive overview showing the potential of MSC therapy as a possible effective treatment strategy for patients with MS.
| S-EPMC10573670 | biostudies-literature
Project description:Mesenchymal stem cells (MSCs) are pluripotent non-hematopoietic precursor cells that can be isolated from bone marrow and numerous other tissues, culture-expanded to purity, and induced to differentiate in vitro and in vivo into mesodermal derivatives. MSCs exhibit many phenotypic and functional similarities to pericytes. The immunomodulatory, tissue protective, and repair-promoting properties of MSCs demonstrated both in vitro and in animal models make them an attractive potential therapy for MS and other conditions characterized by inflammation and/or tissue injury. Other potential advantages of MSCs as a therapeutic include the relative ease of culture expansion, relative immunoprivilege allowing allogeneic transplantation, and their ability to traffic from blood to areas of tissue allowing intravascular administration. The overall published experience with MSC transplantation in MS is modest, but several small case series and preliminary studies yielded promising results. Several groups, including us, recently initiated formal studies of autologous, culture-expanded, bone marrow-derived MSC transplantation in MS. Although there are several potential safety concerns, to date, the procedure has been well tolerated. Future studies that more definitively assess efficacy also will need to address several technical issues.
| S-EPMC3624046 | biostudies-literature
Project description:BackgroundMultiple studies have reported that stem cell therapy has beneficial effects in animal models of intracerebral hemorrhage (ICH). However, this finding remains inconclusive. This study was performed to systematically determine the effect size of stem cell therapy in ICH animal models by pooling and analyzing data from newly published studies.MethodsA literature search identified studies of stem cells in animal models of ICH. We searched mainstream databases from inception to November, 2021. And pooled effect size of stem cells was determined for diversified neurobehavioral scales and structural endpoints using random effects models.ResultsThe median quality score of 62 included studies was 5.32. Our results revealed an overall positive effect of stem cell therapy. More specifically, the SMD was - 2.27 for mNSS, - 2.14 for rotarod test, - 2.06 for MLPT, - 1.33 for cylinder test, - 1.95 for corner turn test, - 1.42 for tissue loss, and - 1.86 for brain water content. For mNSS, classifying comparisons by quality score showed significant differences in estimates of effect size (p = 0.013), and high-quality comparisons showed a better outcome (SMD = - 2.57) compared with low-quality comparisons (SMD = - 1.59). Besides, different delivery routes also showed a significant difference in the estimates of effect size for mNSS (p = 0.002), and the intraperitoneal route showed the best outcome (SMD = - 4.63). For tissue loss, the autologous blood-induced ICH model showed a better outcome (SMD = - 1.84) compared with the collagenase-induced ICH model (SMD = - 0.94, p = 0.035). Additionally, stem cell therapy initiated within 8 h post-ICH showed the greatest efficacy on tissue loss reduction, followed by initiated with 24 h post-ICH. Finally, stem cells with different sources and types showed similar beneficial effects for mNSS as well as tissue loss.ConclusionsOur results suggested that stem cell therapy had remarkable benefits on ICH animals on both the functional and structural outcomes in animal models of ICH, with very large effect size. These findings support the utility of further studies to translate stem cells in the treatment of ICH in humans. Moreover, the results should be interpreted in the light of the limitations in experimental design and the methodological quality of the studies included in the meta-analysis.
| S-EPMC9446670 | biostudies-literature
Project description:Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterized by an aberrant activation of the immune system and combining demyelination with neurodegeneration. Studies on experimental models of multiple sclerosis revealed immunomodulatory and immunosuppressive properties of mesenchymal stem cells. Clinical trials using mesenchymal stem cells therapy in multiple sclerosis patients showed tolerability, safety on short term, some immunomodulatory properties reducing the Th1 proinflammatory response and the inflammatory MRI parameters. The author reviews the data about experimental studies and clinical trials using mesenchymal stem cells for the treatment of multiple sclerosis.
| S-EPMC4397514 | biostudies-other