Dataset Information

Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying MicroRNA-181c-5p Promote BMP2-Induced Repair of Cartilage Injury through Inhibition of SMAD7 Expression.

ABSTRACT: The therapy role of mesenchymal stem cell- (MSC-) derived extracellular vesicles (EVs) in cartilage regeneration has been well studied. Herein, we tried to analyze the role of human umbilical cord MSC- (hUCMSC-) EVs carrying microRNA- (miR-) 181c-5p in repair of cartilage injury. After successful isolation of hUCMSCs, the multidirectional differentiation abilities were analyzed. Then, the EVs were isolated and identified. After coculture of PKH26-labled EVs with bone marrow MSCs (BMSCs), the biological behaviors of which were detected. The relationship between the predicted early posttraumatic osteoarthritis-associated miRNA, miR-181c-5p, and SMAD7 was verified. Gain- and loss-of functions were performed for investing the role of miR-181c-5p and SMAD7 in BMP-induced chondrogenesis in vitro and in vivo. hUCMSC-EVs could be internalized by BMSCs and promote the proliferative, migratory, and chondrogenic differentiation potentials of BMSCs. Additionally, miR-181c-5p could target and inhibit SMAD7 expression to promote the bone morphogenic protein 2- (BMP2-) induced proliferative, migratory, and chondrogenic differentiation potentials of BMSCs. Also, overexpression of SMAD7 inhibited the repairing effect of BMP2, and overexpression of BMP2 and miR-181c-5p further promoted the repair of cartilage injury in vivo. Our present study highlighted the repairing effect of hUCMSC-EVs carrying miR-181c-5p on cartilage injury.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC9249498 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying MicroRNA-181c-5p Promote BMP2-Induced Repair of Cartilage Injury through Inhibition of SMAD7 Expression.

Zhang Qiang Q Cao Le L Zou Shanqi S Feng Yuanling Y Miao Xudong X Huang Lu L Wu Yongping Y

Stem cells international 20220624

The therapy role of mesenchymal stem cell- (MSC-) derived extracellular vesicles (EVs) in cartilage regeneration has been well studied. Herein, we tried to analyze the role of human umbilical cord MSC- (hUCMSC-) EVs carrying microRNA- (miR-) 181c-5p in repair of cartilage injury. After successful isolation of hUCMSCs, the multidirectional differentiation abilities were analyzed. Then, the EVs were isolated and identified. After coculture of PKH26-labled EVs with bone marrow MSCs (BMSCs), the bio ...[more]

PMID: 35782228

Similar Datasets

Project description:Generating insulin-producing cells (IPCs) from human pluripotent stem cells is a promising method for studying the molecular mechanism underlying pancreas development and a potential treatment source for type 1 diabetes. Previous studies have shown that miR-181c-5p is highly enriched in adult islets; however, its role in pancreatic β cell differentiation is poorly understood. In this study, we differentiated human induced pluripotent stem cells (hiPSCs) into IPCs in a stepwise process that recapitulated pancreas organogenesis and observed that miR-181c-5p continuously accumulated throughout the entire differentiation process. hiPSCs were transduced with lentiviral vectors containing human miR-181c-5p precursor, which significantly increased the endodermal markers SOX17, FOXA2, CXCR4 and GATA4 and pancreatic endocrine-specific gene expression, including PDX1, NKX6.1, MAFA and Insulin. miR-181c-5p overexpression exerted little effect on the efficiency of definitive endoderm, whereas it promoted the differentiation of pancreatic progenitors and IPCs, especially for NKX6.1-positive and insulin-positive cells differentiation. Transplanted these cells exhibit glucose-stimulated C-peptide secretion in vivo and protect mice from chemically induced diabetes. It was found that miR-181c-5p directly targets the 3'UTR of smad7 and TGIF2 mRNA, which are known to be endogenous repressors of TGF-β-smad2/3 signaling, to decrease their mRNA and protein levels. Furthermore, overexpressed miR-181c-5p led to an elevation of the smad2/3 phosphorylation levels in hiPSC-derived cells, while treatment with smad2/3 inhibitors following miR-181c-5p overexpression had opposite effects on IPC formation. These results suggest that miR-181c-5p is critically involved in pancreatic lineage commitment through direct repression of smad7 and TGIF2 and that it modulates TGF-β-smad2/3 signaling activation and increases the feasibility of using patient-specific hiPSCs for β cell replacement therapy for type 1 diabetes.

Project description:BackgroundIt has been proposed that the fetus prioritizes iron for hemoglobin production over delivery to tissues. However, few studies have evaluated the interrelations between hemoglobin and multiple iron status biomarkers in umbilical cord blood. A full understanding is needed of how these parameters influence each other within cord blood to fully interpret iron and hematologic status at birth.ObjectivesWe evaluated the determinants of neonatal hemoglobin and assessed the interrelations between hemoglobin, serum iron status indicators, and serum iron regulatory hormones in healthy neonates.MethodsThis was an observational study that assessed umbilical cord hemoglobin (Hb), serum ferritin (SF), erythropoietin (EPO), soluble transferrin receptor (sTfR), serum iron, hepcidin, vitamin B-12, folate, IL-6, and CRP measured in 234 neonates born to adolescents or to women carrying multiples. Correlations between these indicators were evaluated and mediation models consistent with the observed significant determinants of cord Hb concentrations were developed.ResultsA highly significant inverse association was found between cord SF and Hb concentrations that was not attributable to neonatal or maternal inflammation (as measured by IL-6 and CRP). The inverse association was present in the combined cohort, as well as in the adolescent and multiples cohorts independently. Mediation analyses found that EPO and hepcidin had significant indirect effects on cord Hb, associations that are explicable by mediation through SF and sTfR.ConclusionIn contrast to observations made in older infants, a highly significant inverse association between Hb and SF, as well positive associations between Hb and both sTfR and EPO, were observed in umbilical cord blood from neonates born to adolescents or women carrying multiples. These findings, combined with review of the published literature, indicate a need for analysis of the relations between multiple parameters to assess iron and hematologic status at birth. These clinical trials were registered at clinicaltrials.gov as NCT01582802 (https://clinicaltrials.gov/ct2/show/NCT01582802) and NCT01019902 (https://clinicaltrials.gov/ct2/show/NCT01019902).

Dataset Information

Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying MicroRNA-181c-5p Promote BMP2-Induced Repair of Cartilage Injury through Inhibition of SMAD7 Expression.

Publications

Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying MicroRNA-181c-5p Promote BMP2-Induced Repair of Cartilage Injury through Inhibition of SMAD7 Expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets