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1.
Int Immunopharmacol ; 129: 111660, 2024 Mar 10.
Article in English | MEDLINE | ID: mdl-38350357

ABSTRACT

BACKGROUND: Human amniotic mesenchymal stem cells (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammation which makes them suitable for the treatment of various diseases. OBJECTIVE: This study aimed to explore the therapeutic effect and molecular mechanism of hAMSCs in ventricular remodeling (VR). METHODS: hAMSCs were characterized by a series of experiments such as flow cytometric analysis, immunofluorescence, differentiative induction and tumorigenicity. Mouse VR model was induced by isoproterenol (ISO) peritoneally, and the therapeutic effects and the potential mechanisms of hAMSCs transplantation were evaluated by echocardiography, carboxy fluorescein diacetate succinimidyl ester (CFSE) labeled cell tracing, histochemistry, qRT-PCR and western blot analysis. The co-culturing experiments were carried out for further exploring the mechanisms of hAMSCs-derived conditioned medium (CM) on macrophage polarization and fibroblast fibrosis in vitro. RESULTS: hAMSCs transplantation significantly alleviated ISO-induced VR including cardiac hypertrophy and fibrosis with the improvements of cardiac functions. CFSE labeled hAMSCs kept an undifferentiated state in heart, indicating that hAMSCs-mediated the improvement of ISO-induced VR might be related to their paracrine effects. hAMSCs markedly inhibited ISO-induced inflammation and fibrosis, seen as the increase of M2 macrophage infiltration and the expressions of CD206 and IL-10, and the decreases of CD86, iNOS, COL3 and αSMA expressions in heart, suggesting that hAMSCs transplantation promoted the polarization of M2 macrophages and inhibited the polarization of M1 macrophages. Mechanically, hAMSCs-derived CM significantly increased the expressions of CD206, IL-10, Arg-1 and reduced the expressions of iNOS and IL-6 in RAW264.7 macrophages in vitro. Interestingly, RAW264.7-CM remarkably promoted the expressions of anti-inflammatory factors such as IL-10, IDO, and COX2 in hAMSCs. Furthermore, the CM derived from hAMSCs pretreated with RAW264.7-CM markedly inhibited the expressions of fibrogenesis genes such as αSMA and COL3 in 3T3 cells. CONCLUSION: Our results demonstrated that hAMSCs effectively alleviated ISO-induced cardiac hypertrophy and fibrosis, and improved the cardiac functions in mice, and the underlying mechanisms might be related to inhibiting the inflammation and fibrosis during the ventricular remodeling through promoting the polarization of CD206hiIL-10hi macrophages in heart tissues. Our study strongly suggested that by taking the advantages of the potent immunosuppressive and anti-inflammatory effects, hAMSCs may provide an alternative therapeutic approach for prevention and treatment of VR clinically.


Subject(s)
Fluoresceins , Interleukin-10 , Mesenchymal Stem Cells , Succinimides , Mice , Humans , Animals , Interleukin-10/pharmacology , Amnion , Isoproterenol , Ventricular Remodeling , Macrophages , Inflammation/chemically induced , Inflammation/therapy , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Fibrosis , Cardiomegaly
2.
Int Immunopharmacol ; 124(Pt B): 110875, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37742368

ABSTRACT

BACKGROUND: Extensions of mesenchymal stem cells (MSCs) in vitro may lead to the loss of their biological functions. However, hypoxic culturation has been shown to enhance the proliferation, survival, and immunomodulatory capacity of MSCs. OBJECTIVE: We aimed to investigate the effects of long-term hypoxic cultivation on the properties of human umbilical cord-derived MSCs (hUCMSCs) and the therapeutic effects of their extracellular vesicles (EVs) in allergic rhinitis (AR). METHODS: Proliferation, senescence, telomerase activity and multipotent properties of hUCMSCs were analyzed under long-term culturation of hypoxia (1%) or normoxia (21%), and the therapeutic effects of their conditional medium (CM) and EVs were evaluated in OVA-induced AR mice. Effects of hypoxia-EVs (Hy-EVs) or normoxia-EVs (No-EVs) on human monocyte-derived dendritic cells (DCs) were investigated, and the possible mechanisms of Hy-EVs in induction of immunotolerance were further explored. RESULTS: Long-term hypoxia significantly promoted the proliferation, inhibited cell senescence, maintained the multipotent status of hUCMSCs. Hy-CM and Hy-EVs showed better therapeutic effects in AR mice compared to No-EVs, seen as improvement of AR-related behaviors such as rubbing and sneezing, and attenuation of inflammation in nasal tissues. In addition, Hy-EVs significantly reduced the expressions of HLA-DR, CD80, CD40, and CD83 induced by OVA plus LPS in DCs, inhibiting the maturation of DCs. Furthermore, we observed that VEGF was remarkably enriched in Hy-EVs, but not in No-EVs, and the inhibition of DCs maturation was markedly neutralized by VEGF antibodies, suggesting that VEGF derived from Hy-EVs was responsible for the inhibition of DCs maturation. CONCLUSION: Our results demonstrated that long-term hypoxia significantly promoted the proliferation, inhibited cell senescence, maintained the multipotent status of hUCMSCs, and hypoxia treated hUCMSCs-derived EVs enhanced their therapeutic effects in AR mice through VEGF-mediated inhibition of DCs maturation.


Subject(s)
Extracellular Vesicles , Mesenchymal Stem Cells , Rhinitis, Allergic , Humans , Mice , Animals , Vascular Endothelial Growth Factor A/metabolism , Mesenchymal Stem Cells/metabolism , Rhinitis, Allergic/therapy , Rhinitis, Allergic/metabolism , Hypoxia/therapy , Hypoxia/metabolism , Dendritic Cells/metabolism , Extracellular Vesicles/metabolism
3.
BMJ Open ; 12(11): e065795, 2022 11 02.
Article in English | MEDLINE | ID: mdl-36323481

ABSTRACT

INTRODUCTION: An increasing number of studies comparing automated peritoneal dialysis (APD) with continuous ambulatory peritoneal dialysis (CAPD) in clinical outcomes have been published since the publication of a systematic review and meta-analysis including three randomised controlled trials in 2007. We will conduct a systematic review and meta-analysis to explore more clinical outcomes of APD versus CAPD for end-stage kidney disease. METHODS AND ANALYSIS: The protocol is conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Three databases-PubMed, EMBASE and the Cochrane Library-will be searched comprehensively from inception to 16 June 2022, without language restriction. Studies reporting clinical outcomes comparing APD with CAPD will be included. Two independent reviewers will screen the titles and abstracts and then obtain and assess full texts of potential relevant articles for eligibility following the inclusion and exclusion criteria. The methodological quality of included observational studies will be assessed by using the Newcastle-Ottawa Scale. The risk of bias of included randomised controlled studies will be assessed by using the Cochrane Risk of Bias tool. Relative risk for dichotomous outcomes and standard mean difference for continuous outcomes with corresponding 95% CIs will be pooled for summary effects. Cochrane Q test and I 2 values will be used to assess heterogeneity between studies. To assess and explore the source of heterogeneity, subgroup analyses and sensitivity analyses will be conducted, and meta-regression, funnel plot and Egger's test will be performed if there are no less than 10 studies. Analyses will be performed using STATA software, V.13.0 (STATA Corporation, College Station, Texas, USA). ETHICS AND DISSEMINATION: Ethics approval is not applicable as no personal information is collected from patients. The results will be published in a peer-reviewed journal or disseminated in relevant academic conferences. PROSPERO REGISTRATION NUMBER: CRD42022311401.


Subject(s)
Kidney Failure, Chronic , Peritoneal Dialysis, Continuous Ambulatory , Peritoneal Dialysis , Humans , Peritoneal Dialysis/methods , Kidney Failure, Chronic/therapy , Research Design , Texas , Meta-Analysis as Topic , Systematic Reviews as Topic
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