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Efficacy of mesenchymal stem cells in animal models of lupus nephritis: a meta-analysis.

ABSTRACT: BACKGROUND:Lupus nephritis is usually manifested by proteinuria, active urinary sediment, hypertension, and renal failure and is a serious complication with more than 50% occurrence in systemic lupus erythematosus patients. Mesenchymal stem cells (MSC) present remarkable immunomodulatory ability, and these cells are potential therapeutic agents for autoimmune disorders. In clinical trials, the effectiveness of MSC in the treatment of lupus nephritis is still controversial. A meta-analysis was performed to assess whether MSC can achieve good efficacy in the treatment of lupus nephritis in mice. METHODS:A comprehensive literature search was performed in Cochrane Library, ISI Web of Science, PubMed, and EMBASE from inception to Oct 1, 2019. Two authors independently extracted the data, which were pooled and calculated using RevMan 5.3. RESULTS:A total of 28 studies met the inclusion criteria. MSC treatment resulted in lower levels of ds-DNA (OR?=?-?29.58, 95% CI -?29.58, -?17.99; P?

SUBMITTER: Zhou T

PROVIDER: S-EPMC7001209 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Efficacy of mesenchymal stem cells in animal models of lupus nephritis: a meta-analysis.

Zhou Tianbiao T Liao Chunling C Li Hong-Yan HY Lin Wenshan W Lin Shujun S Zhong Hongzhen H

Stem cell research & therapy 20200204 1

<h4>Background</h4>Lupus nephritis is usually manifested by proteinuria, active urinary sediment, hypertension, and renal failure and is a serious complication with more than 50% occurrence in systemic lupus erythematosus patients. Mesenchymal stem cells (MSC) present remarkable immunomodulatory ability, and these cells are potential therapeutic agents for autoimmune disorders. In clinical trials, the effectiveness of MSC in the treatment of lupus nephritis is still controversial. A meta-analysi ...[more]

PMID: 32019582

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Project description:Systemic lupus erythematosus (SLE) is a polymorphic, multisystemic autoimmune disease that causes multiorgan damage in which cellular communication occurs through the involvement of autoantibodies directed against autoantigen production. Mesenchymal stem cells (MSCs), which have strong protective and immunomodulatory abilities, are obtained not only from bone marrow but also from medical waste such as adipose tissue and umbilical cord tissue and have been recognized as a promising tool for the treatment of various autoimmune diseases and inflammatory disorders. This meta-analysis is aimed at assessing whether MSCs can become a new treatment for SLE with good efficacy and safety. Based on predetermined criteria, a bibliographical search was performed from January 1, 2000, to July 31, 2019, by searching the following databases: ISI Web of Science, Embase, PubMed, the Cochrane Library, and the Chinese Biomedical Literature Database (CBM). Eligible studies and data were identified. Statistical analysis was conducted to assess the efficacy (proteinuria, systemic lupus erythematosus disease activity index (SLEDAI), Scr, BUN, albumin, C3, and C4) and safety (rate of adverse events) of MSCs for SLE using Cochrane Review Manager Version 5.3. Ten studies fulfilled the inclusion criteria and were eligible for this meta-analysis, which comprised 8 prospective or retrospective case series and four randomized controlled trails (RCTs) studies. In the RCT, the results indicated that the MSC group had lower proteinuria than the control group at 3 months and 6 months and the MSC group displayed a lower SLEDAI than the control group at 2 months and 6 months. Furthermore, the MSC group showed a lower rate of adverse events than the control group (OR = 0.26, 95% CI: 0.07, 0.89, P = 0.03). In the case series trials, the results indicated that the MSC group had lower proteinuria at 1 month, 2 months, 3 months, 4 months, 6 months, and 12 months. In conclusion, MSCs might be a promising therapeutic agent for patients with SLE.

Project description:IntroductionTreatment with sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to be efficacious in the MRL/lpr and NZB x NZW F1 mouse models of lupus nephritis, indicating a critical role for the mTOR pathway in both models. This type of demonstration of efficacy in animal models is usually a pre-requisite for advancement into clinical development. However, efficacy in an animal model often has not translated to the desired activity in the clinic. Therefore, a more profound understanding of the mechanistic similarities and differences between various animal models and human diseases is highly desirable.MethodsTranscriptional profiling was performed on kidneys from mice with lupus nephritis; from mice who had efficacious drug treatment; and from mice before they developed nephritis. Analysis of variance with false discovery rate adjusted to p < 0.05 and an average fold change of two or more was used to identify transcripts significantly associated with disease and response to therapy. Pathway analyses (using various bioinformatics tools) were carried out to understand the basis for drug efficacy in the mouse model. The relevance in human lupus of the pathways identified in the mouse model was explored using information from several databases derived from the published literature.ResultsWe identified a set of nephritis-associated genes in mouse kidney. Expression of the majority of these returned to asymptomatic levels on sirolimus treatment, confirming the correlation between expression levels and symptoms of nephritis. Network analysis showed that many of these nephritis genes are known to interact with the mTOR pathway. This led us to ask what human diseases are linked to the mTOR pathway. We constructed the mTOR pathway interactome consisting of proteins that interact with members of the mTOR pathway and identified a strong association between mTOR pathway genes and genes reported in the literature as being involved in human lupus.ConclusionsOur findings implicate the mTOR pathway as a critical contributor to human lupus. This broad pathway-based approach to understanding the similarities in, and differences between, animal models and human diseases may have broader utility.

Dataset Information

Efficacy of mesenchymal stem cells in animal models of lupus nephritis: a meta-analysis.

Publications

Efficacy of mesenchymal stem cells in animal models of lupus nephritis: a meta-analysis.

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