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Project description:Background and aim: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints. Synovial fibroblasts (SFs) play a key role in the pathogenesis of RA. Dysregulation of MicroRNAs (miRNAs) expression in SFs mediates the development of RA. Exosomes (Exos) can transfer miRNAs between cells and have been validated as carriers for the delivery of therapeutic molecules.This study aimed toinvestigate the therapeutic potential of human umbilical cord mesenchymal stem cells (hUCMSC)-Exos deliveringmiR-451a to regulate ATF2 for RA both in vivo and in vitro. Methods: In this study, hUCMSC and RASF were isolated and identified, and hUCMSC-EXOs were extracted and characterized. The influence of hUCMSC-Exos on RASF was detected. hUCMSC-Exos RNA was labeled and hUCMSC-Exos targeting RA-SFs was traced. AGO2 promoted miRNA maturation, and hUCMSCKD-AGO2 was prepared by knocking down AGO2 in hUCMSC. hUCMSCKD-AGO2-Exos was extracted and characterized,and their influence on RASFs was detected. mRNA and miRNA profiles before and after hUCMSC-Exos intervention in RASFs were mapped to identify differential miRNAs. RT-qPCR was used to verify the differential miRNAs, with miR-451a finally selected as the target gene.The effect of miR-451a on SFs was detected. The latent binding of miR-451a to activating transcription factor 2 (ATF2)was analyzed. The effect of hUCMSC-ExosmiR-451a on SFs was detected, and the expression of miR-451a and ATF2 was measured by RT-PCR.In vivo, hUCMSC-ExosmiR-451a was injected into the ankle joint of CIA rats, and arthritis index, joint imaging and synovial pathology were assessed. The expression of miR-451a and ATF2 in synovial tissue was detected. Finally, the safety of hUCMSC-ExosmiR-451a in CIA rats was evaluated. Results: This study revealed that hUCMSC-Exos can inhibit RASF proliferation, migration and invasion through miRNAs. High throughput sequencing detected 13 miRNAs that could be transmitted from hUCMSC to RASF via hUCMSC-EXOs. MiR-451a inhibited RASF proliferation, migration and invasion by regulating ATF2. hUCMSC-Exos loaded with miR-451a targeted ATF2 to inhibit RASF proliferation, migration and invasion, and improve joint inflammation and imaging findings in CIA rats. Conclusions: This study demonstrates that miR-451a carried by hUCMSC-Exos canplay a role ininhibiting RASF biological traits and improving arthritis in CIA rats by inhibiting ATF2. The findings study suggest a promising treatment for RA and provide insights into the mechanism of action of hUCMSC-Exo in RA.
2025-04-29 | GSE237991 | GEO
Project description:Background and aim: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints. Synovial fibroblasts (SFs) play a key role in the pathogenesis of RA. Dysregulation of MicroRNAs (miRNAs) expression in SFs mediates the development of RA. Exosomes (Exos) can transfer miRNAs between cells and have been validated as carriers for the delivery of therapeutic molecules.This study aimed toinvestigate the therapeutic potential of human umbilical cord mesenchymal stem cells (hUCMSC)-Exos deliveringmiR-451a to regulate ATF2 for RA both in vivo and in vitro. Methods: In this study, hUCMSC and RASF were isolated and identified, and hUCMSC-EXOs were extracted and characterized. The influence of hUCMSC-Exos on RASF was detected. hUCMSC-Exos RNA was labeled and hUCMSC-Exos targeting RA-SFs was traced. AGO2 promoted miRNA maturation, and hUCMSCKD-AGO2 was prepared by knocking down AGO2 in hUCMSC. hUCMSCKD-AGO2-Exos was extracted and characterized,and their influence on RASFs was detected. mRNA and miRNA profiles before and after hUCMSC-Exos intervention in RASFs were mapped to identify differential miRNAs. RT-qPCR was used to verify the differential miRNAs, with miR-451a finally selected as the target gene.The effect of miR-451a on SFs was detected. The latent binding of miR-451a to activating transcription factor 2 (ATF2)was analyzed. The effect of hUCMSC-ExosmiR-451a on SFs was detected, and the expression of miR-451a and ATF2 was measured by RT-PCR.In vivo, hUCMSC-ExosmiR-451a was injected into the ankle joint of CIA rats, and arthritis index, joint imaging and synovial pathology were assessed. The expression of miR-451a and ATF2 in synovial tissue was detected. Finally, the safety of hUCMSC-ExosmiR-451a in CIA rats was evaluated. Results: This study revealed that hUCMSC-Exos can inhibit RASF proliferation, migration and invasion through miRNAs. High throughput sequencing detected 13 miRNAs that could be transmitted from hUCMSC to RASF via hUCMSC-EXOs. MiR-451a inhibited RASF proliferation, migration and invasion by regulating ATF2. hUCMSC-Exos loaded with miR-451a targeted ATF2 to inhibit RASF proliferation, migration and invasion, and improve joint inflammation and imaging findings in CIA rats. Conclusions: This study demonstrates that miR-451a carried by hUCMSC-Exos canplay a role ininhibiting RASF biological traits and improving arthritis in CIA rats by inhibiting ATF2. The findings study suggest a promising treatment for RA and provide insights into the mechanism of action of hUCMSC-Exo in RA.
2025-04-29 | GSE237992 | GEO
Project description:Human umbilical cord mesenchymal stem cell-derived exosomes deliver miRNA-451a targeting ATF2 to inhibit rheumatoid arthritis.
| PRJNA997346 | ENA
Project description:Human umbilical cord mesenchymal stem cell-derived exosomes deliver miRNA-451a targeting ATF2 to inhibit rheumatoid arthritis [RNA-seq]
| PRJNA997350 | ENA
Project description:Human umbilical cord mesenchymal stem cell-derived exosomes deliver miRNA-451a targeting ATF2 to inhibit rheumatoid arthritis [small RNA-seq]
| PRJNA997349 | ENA
Project description:BackgroundIntervertebral disc degeneration (IVDD) is the breakdown of the discs supporting the vertebrae. It is one of the most frequent causes of back pain worldwide. Currently, the clinical interventions for IVDD are mainly focused on symptom releases. Thus, new therapeutic options are needed.MethodsNucleus pulposus (NP) samples were obtained from 20 patients experiencing IVDD and 10 healthy volunteers compared for mRNA N6-methyladenosine (m6A) mRNA modification as well as methyltransferase (METT) like METTL3, METTL14, and Wilms' tumor 1-associated protein mRNA and protein abundance following exosomes exposure from mesenchymal stem cells. In addition, microRNA expressions were also compared. The correlation between the NLR family pyrin domain containing 3 (NLRP3) and METTL14 was measured by luciferase reporter assay. Cytokines were evaluated using an enzyme-linked immunosorbent assay. METTL14, NLRP3, and insulin-like growth factor 2 mRNA-binding protein 2 mRNAs were measured via a quantitative reverse transcription-polymerase chain reaction. Protein was assayed using western blots. Cell death was assessed by propidium iodide staining, lactate dehydrogenase release, gasdermin-N domain abundance, and caspase-1 activation.ResultsThe human umbilical cord mesenchymal stem cell (hucMSC) exosomes were found to effectively improve the viability of NP cells and protect them from pyroptosis through targeting METTL14, with a methyltransferase catalyzing m6A modification. METTL14 was highly present in NP cells from IVDD patients, which stabilize NLRP3 mRNA in an IGFBP2-dependent manner. The elevated NLRP3 levels result in the increase of interleukin 1β (IL-1β) and IL-18 levels and trigger pyroptotic NP cell death. Such pathogenic axis could be blocked by hucMSC exosomes, which directly degrade METTL14 through exosomal miR-26a-5p.ConclusionsThe results of the current study revealed the beneficial effects of hucMSC exosomes on NP cells and determined a potential mechanism inducing IVDD.
| S-EPMC8375162 | biostudies-literature
Project description:Cervus and cucumis peptides (Lugua polypeptides, LG) are traditional Chinese medicine, which are active components of polypeptide extracted from Sika deer bone and melon seed, and they contain bone induced polypeptide biological factors. Umbilical cord mesenchymal stem cell, (UC-MSC) have tissue repair multiple effects, anti-inflammatory, and immune regulation function, which become a very promising start in rheumatoid arthritis (RA) treatment. Hence, LG combined UC-MSC can significantly enhance the UC-MSC treatment of rheumatoid arthritis (RA).To explore the clinical curative effect and therapeutic mechanism of LG combined UC-MSC for treating RA.119 patients were divided into control and treatment groups, and both groups were treated with methotrexate tablets, leflunomide, and UC-MSC. But, LG were added to the treatment group. In vitro, the effects of LG on UC-MSC cell secretion of anti-inflammatory factors were also performed.The Health Assessment Questionnaire; the 28 joint disease activity score; C reactive protein; the erythrocyte sedimentation rate; rheumatoid factor; and anti-cyclic citrullinated peptide antibody were significantly reduced in treatment group 1 year after treatment (P < .05). In vitro, compared with the control group, the number of hepatocyte growth factor (HGF), the secretion of prostaglandin E2 (PGE2) and tumor necrosis factor-inducible gene 6 protein (TSG6) increased significantly (P < .05).LG combined UC-MSCs can significantly improve the curative effect of RA patients, while LG may reduce inflammatory cytokines, regulate immunity, improve microcirculation, and are conducive to UC-MSCs migration and the repair of damaged tissue.
| S-EPMC7360298 | biostudies-literature
Project description:Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology with a high rate of disability. Traditional treatments for RA remain a challenging issue. For example, nonsteroidal anti-inflammatory drugs (NSAIDs) have no therapeutic effects on joint destruction, and the prominent side effects include gastrointestinal symptoms. RA is characterized by recurrence and bone attrition. Therefore, regenerative medicine and the use of umbilical cord mesenchymal stem cell (UC-MSC) therapies have recently emerged as potential options. UC-MSCs are multifunctional stem cells that are present in neonatal umbilical cord tissue and can differentiate into many kinds of cells, which have broad clinical application prospects in the tissue engineering of bone, cartilage, muscle, tendon, ligament, nerve, liver, endothelium, and myocardium. Moreover, UC-MSCs have advantages, such as convenient collection of materials and no ethical disputes; thus, these cells have attracted increasing attention from researchers. However, there are few clinical studies regarding UC-MSC therapy for RA. In this paper, we will review traditional drugs for RA treatment and then focus on UC-MSC therapy for RA, including preclinical and clinical UC-MSC applications for RA patients in the context of regenerative medicine. Finally, we will summarize the challenges and perspectives of UC-MSCs as a potential therapeutic strategy for RA. This review will help to design and discover more potent and efficacious treatments for RA patients and aid in advancing this class of cell therapy.
| S-EPMC8462093 | biostudies-literature
Project description:BackgroundExosomal microRNAs (miRNAs or miRs) from bone marrow-derived mesenchymal stem cells (UCMSCs) have emerged as promising therapeutic strategies for cancer treatment. The current study aimed to elucidate the underlying mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs)-derived exosomal miR-375 in esophageal squamous cell carcinoma (ESCC).MethodsAfter determining the expression of miR-375 and its putative target enabled homolog (ENAH) in ESCC tissues and cells, we tested effects of their altered expression on ESCC proliferation, invasion, migration, and tumorsphere formation was subsequently measured. Transfected hUCMSCs-derived exosomes (hUCMSCs-exo) were isolated and co-cultured with ESCC cells to measure the effects of miR-375 delivered by hUCMSCs-exo on ESCC development. Finally, we investigated the effect of miR-375 on tumor growth in vivo.ResultsThe expression of miR-375 was reduced, while the expression of ENAH was elevated in ESCC. ENAH was identified as a target gene of miR-375. Elevated miR-375 or depleted ENAH expression inhibited ESCC cell proliferation, invasion, migration, tumorsphere formation, and promoted apoptosis. Moreover, miR-375 delivered by hUCMSCs-exo could suppress ESCC cell proliferation, invasion, migration, tumorsphere formation, but promoted apoptosis in vitro, as well as inhibiting tumor growth in vivo.ConclusionsTaken together, hUCMSCs-exo can deliver miR-375 to suppress ENAH expression and subsequently inhibit the initiation and progression of ESCC.
| S-EPMC7374920 | biostudies-literature
Project description:BackgroundTesticular aging is associated with diminished fertility and certain age-related ailments, and effective therapeutic interventions remain elusive. Here, we probed the therapeutic efficacy of exosomes derived from human umbilical cord mesenchymal stem cells (hUMSC-Exos) in counteracting testicular aging.MethodsWe employed a model of 22-month-old mice and administered intratesticular injections of hUMSC-Exos. Comprehensive analyses encompassing immunohistological, transcriptomic, and physiological assessments were conducted to evaluate the effects on testicular aging. Concurrently, we monitored alterations in macrophage polarization and the oxidative stress landscape within the testes. Finally, we performed bioinformatic analysis for miRNAs in hUMSC-Exos.ResultsOur data reveal that hUMSC-Exos administration leads to a marked reduction in aging-associated markers and cellular apoptosis while promoting cellular proliferation in aged testis. Importantly, hUMSC-Exos facilitated the restoration of spermatogenesis and elevated testosterone synthesis in aged mice. Furthermore, hUMSC-Exos could attenuate inflammation by driving the phenotypic shift of macrophages from M1 to M2 and suppress oxidative stress by reduced ROS production. Mechanistically, these efficacies against testicular aging may be mediated by hUMSC-Exos miRNAs.ConclusionsOur findings suggest that hUMSC-Exos therapy presents a viable strategy to ameliorate testicular aging, underscoring its potential therapeutic significance in managing testicular aging.
| S-EPMC10813320 | biostudies-literature