Dataset Information

Meta-analysis of preclinical studies of mesenchymal stromal cells to treat rheumatoid arthritis.

ABSTRACT:

Background

This study aims to evaluate the quality of preclinical data, determine the effect sizes, and identify experimental measures that inform efficacy using mesenchymal stromal (or stem) cells (MSC) therapy in animal models of rheumatoid arthritis (RA).

Methods

Literature searches were performed on MSC preclinical studies to treat RA. MSC treatment effect sizes were determined by the most commonly used outcome measures, including paw thickness, clinical score, and histological score.

Findings

A total of 48 studies and 94 treatment arms were included, among which 42 studies and 79 treatment arms reported that MSC improved outcomes. The effect sizes of RA treatments using MSC, when compared to the controls, were: paw thickness was ameliorated by 53.6% (95% confidence interval (CI): 26.7% -80.4%), histological score was decreased by 44.9% (95% CI: 33.3% -56.6%), and clinical score was decreased by 29.9% (95% CI: 16.7% -43.0%). Specifically, our results indicated that human umbilical cord derived MSC led to large improvements of the clinical score (-42.1%) and histological score (-51.4%).

Interpretation

To the best of our knowledge, this meta-analysis is to quantitatively answer whether MSC represent a robust RA treatment in animal models. It suggests that in preclinical studies, MSC have consistently exhibited therapeutic benefits. The findings demonstrate a need for considering variations in different animal models and treatment protocols in future studies using MSC to treat RA in humans to maximise the therapeutic gains in the era of precision medicine.

Funds

NIH [1DP2CA195763], Baylx Inc.: BI-206512, NINDS/NIH Training Grant [Award# NS082174].

SUBMITTER: Liu L

PROVIDER: S-EPMC6796567 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Meta-analysis of preclinical studies of mesenchymal stromal cells to treat rheumatoid arthritis.

Liu Linan L Wong Chi W CW Han Menglu M Farhoodi Henry P HP Liu Guangyang G Liu Yongjun Y Liao Wenbin W Zhao Weian W

EBioMedicine 20190906

<h4>Background</h4>This study aims to evaluate the quality of preclinical data, determine the effect sizes, and identify experimental measures that inform efficacy using mesenchymal stromal (or stem) cells (MSC) therapy in animal models of rheumatoid arthritis (RA).<h4>Methods</h4>Literature searches were performed on MSC preclinical studies to treat RA. MSC treatment effect sizes were determined by the most commonly used outcome measures, including paw thickness, clinical score, and histologica ...[more]

PMID: 31501076

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Project description:Extreme prematurity is the leading cause of death among children under 5 years of age. Currently, there is no treatment for bronchopulmonary dysplasia (BPD), the most common complication of extreme prematurity. Experimental studies in animal models of BPD suggest that mesenchymal stromal cells (MSCs) are lung protective. To date, no systematic review and meta-analysis has evaluated the preclinical evidence of this promising therapy. Our protocol was registered with Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies prior to searching MEDLINE (1946 to June 1, 2015), Embase (1947 to 2015 Week 22), Pubmed, Web of Science, and conference proceedings (1990 to present) for controlled comparative studies of neonatal animal models that received MSCs or cell free MSC-derived conditioned media (MSC-CM). Lung alveolarization was the primary outcome. We used random effects models for data analysis and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. We screened 990 citations; 25 met inclusion criteria. All used hyperoxia-exposed neonatal rodents to model BPD. MSCs significantly improved alveolarization (Standardized mean difference of -1.330, 95% confidence interval [CI -1.724, -0.94, I2 69%]), irrespective of timing of treatment, source, dose, or route of administration. MSCs also significantly ameliorated pulmonary hypertension, lung inflammation, fibrosis, angiogenesis, and apoptosis. Similarly, MSC-CM significantly improved alveolarization, angiogenesis, and pulmonary artery remodeling. MSCs, tested exclusively in hyperoxic rodent models of BPD, show significant therapeutic benefit. Unclear risk of bias and incomplete reporting in the primary studies highlights nonadherence to reporting standards. Overall, safety and efficacy in other species/large animal models may provide useful information for guiding the design of clinical trials. Stem Cells Translational Medicine 2017;6:2079-2093.

Project description:INTRODUCTION:Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating neurologic condition with high mortality rates and long-term complications for surviving infants. Mesenchymal stem/stromal cells (MSCs) have emerged as novel therapeutic agents with promising results in experimental studies of HIE. The purpose of this study is to (a) methodically review the current preclinical literature describing MSC therapy in animal models of HIE, (b) quantify the effect size in regards to functional neurologic outcome, and (c) identify research gaps/limitations that should be addressed prior to future preclinical and clinical studies. METHODS:Adhering to the Systematic Review Protocol for Animal Intervention Studies, a systematic search of English articles was performed. Eligible studies were identified and data regarding study characteristics and outcome measures was extracted. After quality assessment, meta-analysis and meta-regression were performed to generate random effect size using standardized mean difference (SMD). Funnel plots and Egger's tests were utilized to evaluate for the presence of publication bias. RESULTS:A total of 19 studies met inclusion in the current systematic review. Meta-analysis revealed that MSCs have a significant positive effect on neurobehavioral outcome following HIE injury. Sensorimotor function was improved by 2.25 SMD (95% CI; 2.04-2.46) in cylinder rearing and 2.97 SMD (95% CI; 2.56-3.38) in rotarod. Likewise, cognitive function was improved by 2.76 SMD (95% CI; 2.53-2.98) on the water maze and 2.97 SMD (95% CI; 2.58-3.35) in object recognition. Stratification demonstrated an increased effect size depending on various study characteristics. CONCLUSIONS:Overall, these results suggest a promising role for MSCs in preclinical studies of HIE. MSC treatment demonstrates improved functional outcomes that are encouraging for future translational studies. While risk of bias and heterogeneity limited the strength of our meta-analysis, our results are consistent with those seen in this field of research.

Project description:BackgroundIntestinal ischemia-reperfusion injury (IRI) causes localized and distant tissue lesions. Multiple organ failure is a common complication of severe intestinal IRI, leading to its high rates of morbidity and mortality. Thus far, this is poorly treated, and there is an urgent need for new more efficacious treatments. This study evaluated the beneficial effects of mesenchymal stem cells (MSCs) therapy on intestinal IRI using many animal experiments.MethodsWe conducted a comprehensive literature search from 4 databases: Pubmed, Embase, Cochrane library, and Web of science. Primary outcomes included the survival rate, Chiu's score, intestinal levels of IL-6, TNF-α and MDA, as well as serum levels of DAO, D-Lactate, and TNF-α. Statistical analysis was carried out using Review Manager 5.3.ResultsIt included Eighteen eligible researches in the final analysis. We demonstrated that survival rates in animals following intestinal IRI were higher with MSCs treatment compared to vehicle treatment. Besides, MSCs treatment attenuated intestinal injury caused by IRI, characterized by lower Chiu's score (- 1.96, 95% CI - 2.72 to - 1.19, P < 0.00001), less intestinal inflammation (IL-6 (- 2.73, 95% CI - 4.19 to - 1.27, P = 0.0002), TNF-α (- 3.00, 95% CI - 4.74 to - 1.26, P = 0.0007)) and oxidative stress (MDA (- 2.18, 95% CI - 3.17 to - 1.19, P < 0.0001)), and decreased serum levels of DAO (- 1.39, 95% CI - 2.07 to - 0.72, P < 0.0001), D-Lactate (- 1.54, 95% CI - 2.18 to - 0.90, P < 0.00001) and TNF-α (- 2.42, 95% CI - 3.45 to - 1.40, P < 0.00001). The possible mechanism for MSCs to treat intestinal IRI might be through reducing inflammation, alleviating oxidative stress, as well as inhibiting the apoptosis and pyroptosis of the intestinal epithelial cells.ConclusionsTaken together, these studies revealed that MSCs as a promising new treatment for intestinal IRI, and the mechanism of which may be associated with inflammation, oxidative stress, apoptosis, and pyroptosis. However, further studies will be required to confirm these findings.

Dataset Information

Meta-analysis of preclinical studies of mesenchymal stromal cells to treat rheumatoid arthritis.

Background

Methods

Findings

Interpretation

Funds

Publications

Meta-analysis of preclinical studies of mesenchymal stromal cells to treat rheumatoid arthritis.

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