International journal of stem cells最新文献

{"title":"LIPUS Promotes Endothelial Differentiation and Angiogenesis of Periodontal Ligament Stem Cells by Activating Piezo1.","authors":"Rui Hu,&nbsp;Zheng-Yan Yang,&nbsp;Yue-Heng Li,&nbsp;Zhi Zhou","doi":"10.15283/ijsc22024","DOIUrl":"https://doi.org/10.15283/ijsc22024","url":null,"abstract":"<p><strong>Background and objectives: </strong>Low-intensity pulsed ultrasound (LIPUS) promotes differentiation and regulates biological functions of various stem cells, but its effect on the endothelial differentiation of periodontal ligament stem cells (PDLSCs) is unclear. This study investigated the effect of LIPUS on endothelial differentiation and angiogenesis in PDLSCs and the role of the mechanically sensitive ion channel <i>Piezo1</i> in this process.</p><p><strong>Methods and results: </strong>PDLSCs obtained from healthy people were used for endothelial induction, and 10 <i>μ</i>g/ml lipopolysaccharide (LPS) was used to simulate the inflammatory state. The induced cells were treated with LIPUS (50 mW/cm², 1.5 MHz) to study its effect on the endothelial differentiation of PDLSCs and the tube formation of differentiated cells. PCR, flow cytometry, immunofluorescence, and Matrigel tube formation assays were used to detect the differentiation and tube formation of PDLSCs. GsMTx4 was used to inhibit the expression of Piezo1, and the role of the Piezo1 pathway in the endothelial differentiation and microvascular formation of PDLSCs after LIPUS treatment was studied. The data showed that LIPUS increased endothelial differentiation and angiogenesis in PDLSCs under inflammatory or noninflammatory conditions. The use of an inhibitor weakened the effect of LIPUS.</p><p><strong>Conclusions: </strong>This study demonstrated that LIPUS can activate the expression of Piezo1 and promote the endothelial differentiation and microvascular formation of PDLSCs.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/04/a9/ijsc-15-4-372.PMC9705156.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40406879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NBCe1 Regulates Odontogenic Differentiation of Human Dental Pulp Stem Cells via NF-<i>κ</i>B.","authors":"Qin Li,&nbsp;Yanqin Ju,&nbsp;Changlong Jin,&nbsp;Li Liu,&nbsp;Shouliang Zhao","doi":"10.15283/ijsc21240","DOIUrl":"https://doi.org/10.15283/ijsc21240","url":null,"abstract":"<p><strong>Background and objectives: </strong>Dental pulp stem cells (DPSCs) play an important role in the repair of tooth injuries. Electrogenic sodium bicarbonate cotransporter 1 (NBCe1) is a Na^＋-coupled HCO₃^- transporter encoded by the solute carrier 4A4 (<i>SLC4A4</i>) gene and plays a crucial role in maintaining the pH of DPSCs. Our previous research confirmed that NBCe1 is highly expressed in odontoblasts during the development of the tooth germ. Therefore, in this study, we aimed to investigate the effect of NBCe1 on odontogenic differentiation of DPSCs and further clarify the underlying mechanisms.</p><p><strong>Methods and results: </strong>DPSCs were isolated and identified, and the selective NBCe1 inhibitor S0859 was used to treat DPSCs. We used a cell counting Kit-8 assay to detect cell proliferative ability, and intracellular pH was assessed using confocal microscopy. Odontogenic differentiation of DPSCs was analyzed using real-time PCR and Alizarin Red S staining, and the NF-<i>κ</i>B pathway was assessed using western blotting. Our results indicated that 10 <i>μ</i>M S0859 was the optimal concentration for DPSC induction. Intracellular pH was decreased upon treatment with S0859. The mRNA expressions of <i>DSPP, DMP1, RUNX2, OCN</i>, and <i>OPN</i> were upregulated in the NBCe1 inhibited group compared to the controls. Moreover, NBCe1 inhibition significantly activated the NF-<i>κ</i>B pathway, and a NF-<i>κ</i>B inhibitor reduced the effect of NBCe1 on DPSC differentiation.</p><p><strong>Conclusions: </strong>NBCe1 inhibition significantly promotes odontogenic differentiation of DPSCs, and this process may be regulated by activating the NF-<i>κ</i>B signaling pathway.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/62/c9/ijsc-15-4-384.PMC9705152.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40409643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic Comparison Analysis between Ameloblastoma and AM-1 Cell Line.","authors":"Shujin Li,&nbsp;Dong-Joon Lee,&nbsp;Hyun-Yi Kim,&nbsp;Hidemitsu Harada,&nbsp;Young-Soo Jung,&nbsp;Han-Sung Jung","doi":"10.15283/ijsc22132","DOIUrl":"https://doi.org/10.15283/ijsc22132","url":null,"abstract":"<p><p>Cancer initiation and progression are profoundly along with the crosstalk between cancer cells and the surrounding stroma. Accumulating evidence has shown that the therapy targeting the extracellular matrix (ECM) would regress tumor growth and invasion in the most common carcinomas. However, it remains largely unexplored in several rare tumors like odontogenic tumors. Ameloblastoma (AM) is the representative odontogenic epithelial tumor in the jawbone, and it usually infiltrates into adjacent bone marrow and has unlimited growth capacity and a high potential for recurrence. This study aims to investigate the role of collagen-rich ECM during the invasion of AM. Transcriptomic analysis revealed that ECM- and epithelial-to-mesenchymal transition (EMT)-related genes were up-regulated in AM compared to ameloblastoma cell line, AM-1. Tumoroid forming analysis showed that Collagen-rich ECM is indispensable for AM progression, especially for aggressive growth patterns and collective invasion.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/05/ijsc-15-4-415.PMC9705150.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40654859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MSCs-Derived miR-150-5p-Expressing Exosomes Promote Skin Wound Healing by Activating PI3K/AKT Pathway through PTEN.","authors":"Cheng Xiu,&nbsp;Huining Zheng,&nbsp;Manfei Jiang,&nbsp;Jiaxu Li,&nbsp;Yanhong Zhou,&nbsp;Lan Mu,&nbsp;Weisong Liu","doi":"10.15283/ijsc21135","DOIUrl":"https://doi.org/10.15283/ijsc21135","url":null,"abstract":"<p><strong>Background and objectives: </strong>The goal of this study was to investigate the mechanism of mesenchymal stem cell (MSC)-derived microRNA (miR)-150-5p-expressing exosomes in promoting skin wound healing through activating PI3K/AKT pathway by PTEN.</p><p><strong>Methods and results: </strong>Human umbilical cord (HUC)-MSCs were infected with miR-150-5p overexpression and its control lentivirus, and HUC-MSCs-derived exosomes (MSCs-Exos) with stable expression of miR-150-5p were obtained. HaCaT cells were induced by H₂O₂ to establish a cellular model of skin injury, in which the expression of miR-150-5p and PTEN and the phosphorylation of PI3K and AKT were evaluated. HaCaT cells were transfected with pcDNA3.1-PTEN or pcDNA3.1 and then cultured with normal exosomes or exosomes stably expressing miR-150-5p. Cell proliferation was inspected by CCK-8. Cell migration was detected by scratch test and cell apoptosis by flow cytometry. The starBase tool was used to predict the binding site of miR-150-5p to PTEN. Dual-luciferase reporter assay and RIP assay were applied to assess the interaction between miR-150-5p and PTEN. In H₂O₂-induced HaCaT cells, the miR-150-5p expression decreased, and PTEN expression increased in a concentration-dependent manner. MSCs-Exos promoted the growth and migration of H₂O₂-induced HaCaT cells and inhibited their apoptosis. In addition, overexpression of exosomal miR-150-5p enhanced the protective effect of MSCs-Exos on H₂O₂-induced HaCaT cells; PTEN overexpression in HaCaT cells partially restrained miR-150-5p-mediated inhibition on H₂O₂-induced injury in HaCaT cells. PTEN was a target gene of miR-150-5p. MiR-150-5p regulated PI3K/AKT pathway through PTEN.</p><p><strong>Conclusions: </strong>MSCs-derived miR-150-5p-expressing exosomes promote skin wound healing by activating PI3K/AKT pathway through PTEN.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/65/ijsc-15-4-359.PMC9705155.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40409640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of Urothelial Cells from Mouse-Induced Pluripotent Stem Cells.","authors":"Dongxu Zhang,&nbsp;Fengze Sun,&nbsp;Huibao Yao,&nbsp;Di Wang,&nbsp;Xingjun Bao,&nbsp;Jipeng Wang,&nbsp;Jitao Wu","doi":"10.15283/ijsc21250","DOIUrl":"https://doi.org/10.15283/ijsc21250","url":null,"abstract":"<p><strong>Background and objectives: </strong>The search for a suitable alternative for urethral defect is a challenge in the field of urethral tissue engineering. Induced pluripotent stem cells (iPSCs) possess multipotential for differentiation. The <i>in vitro</i> derivation of urothelial cells from mouse-iPSCs (miPSCs) has thus far not been reported. The purpose of this study was to establish an efficient and robust differentiation protocol for the differentiation of miPSCs into urothelial cells.</p><p><strong>Methods and results: </strong>Our protocol made the visualization of differentiation processes of a 2-step approach possible. We firstly induced miPSCs into posterior definitive endoderm (DE) with glycogen synthase kinase-3<i>β</i> (GSK3<i>β</i>) inhibitor and Activin A. We investigated the optimal conditions for DE differentiation with GSK3<i>β</i> inhibitor treatment by varying the treatment time and concentration. Differentiation into urothelial cells, was directed with all-trans retinoic acid (ATRA) and recombinant mouse fibroblast growth factor-10 (FGF-10). Specific markers expressed at each stage of differentiation were validated by flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR) assay, immunofluorescence staining, and western blotting Assay. The miPSC-derived urothelial cells were successfully in expressed urothelial cell marker genes, proteins, and normal microscopic architecture.</p><p><strong>Conclusions: </strong>We built a model of directed differentiation of miPSCs into urothelial cells, which may provide the evidence for a regenerative potential of miPSCs in preclinical animal studies.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d0/fe/ijsc-15-4-347.PMC9705153.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40406878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lupus Heart Disease Modeling with Combination of Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Lupus Patient Serum.","authors":"Narae Park,&nbsp;Yeri Alice Rim,&nbsp;Hyerin Jung,&nbsp;Yoojun Nam,&nbsp;Ji Hyeon Ju","doi":"10.15283/ijsc21158","DOIUrl":"https://doi.org/10.15283/ijsc21158","url":null,"abstract":"<p><strong>Background and objectives: </strong>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease mainly affecting young women of childbearing age. SLE affects the skin, joints, muscles, kidneys, lungs, and heart. Cardiovascular complications are common causes of death in patients with SLE. However, the complexity of the cardiovascular system and the rarity of SLE make it difficult to investigate these morbidities. Patient-derived induced pluripotent stem cells (iPSCs) serve as a novel tool for drug screening and pathophysiological studies in the absence of patient samples.</p><p><strong>Methods and results: </strong>We differentiated CMs from HC- and SLE-iPSCs using 2D culture platforms. SLE-CMs showed decreased proliferation and increased levels of fibrosis and hypertrophy marker expression; however, HC-and SLE-monolayer CMs reacted differently to SLE serum treatment. HC-iPSCs were also differentiated into CMs using 3D spheroid culture and anti-Ro autoantibody was treated along with SLE serum. 3D-HC-CMs generated more mature CMs compared to the CMs generated using 2D culture. The treatment of anti-Ro autoantibody rapidly increased the gene expression of fibrosis, hypertrophy, and apoptosis markers, and altered the calcium signaling in the CMs.</p><p><strong>Conclusions: </strong>iPSC derived cardiomyocytes with patient-derived serum, and anti-Ro antibody treatment could serve in effective autoimmune disease modeling including SLE. We believe that the present study might briefly provide possibilities on the application of a combination of patient-derived materials and iPSCs in disease modeling of autoimmune diseases.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/84/d0/ijsc-15-3-233.PMC9396017.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39648600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YBX1 Promotes the Inclusion of RUNX2 Alternative Exon 5 in Dental Pulp Stem Cells.","authors":"Jiaoxiang Shen,&nbsp;Wenting She,&nbsp;Fengxia Zhang,&nbsp;Jihua Guo,&nbsp;Rong Jia","doi":"10.15283/ijsc21035","DOIUrl":"https://doi.org/10.15283/ijsc21035","url":null,"abstract":"<p><strong>Background and objectives: </strong>RUNX2 plays an essential role during the odontoblast differentiation of dental pulp stem cells (DPSCs). RUNX2 Exon 5 is an alternative exon and essential for RUNX2 transcriptional activity. This study aimed to investigate the regulatory mechanisms of RUNX2 exon 5 alternative splicing in human DPSCs.</p><p><strong>Methods and results: </strong>The regulatory motifs of RUNX2 exon 5 were analyzed using the online SpliceAid program. The alternative splicing of RUNX2 exon 5 in DPSCs during mineralization-induced differentiation was analyzed by RT-PCR. To explore the effect of splicing factor YBX1 on exon 5 alternative splicing, gaining or losing function of YBX1 was performed by transfection of YBX1 overexpression plasmid or anti-YBX1 siRNA in DPSCs. Human RUNX2 exon 5 is evolutionarily conserved and alternatively spliced in DPSCs. There are three potential YBX1 binding motifs in RUNX2 exon 5. The inclusion of RUNX2 exon 5 and YBX1 expression level increased significantly during mineralization- induced differentiation in DPSCs. Overexpression of YBX1 significantly increased the inclusion of RUNX2 exon 5 in DPSCs. In contrast, silence of YBX1 significantly reduced the inclusion of exon 5 and the corresponding RUNX2 protein expression level. Knockdown of YBX1 reduced the expression of alkaline phosphatase (ALP) and osteocalcin (OC) and the mineralization ability of DPSCs, while overexpression of YBX1 increased the expression of ALP and OC and the mineralization ability of DPSCs.</p><p><strong>Conclusions: </strong>Human RUNX2 exon 5 is conserved evolutionarily and alternatively spliced in DPSCs. Splicing factor YBX1 promotes the inclusion of RUNX2 exon 5 and improves the mineralization ability of DPSCs.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/36/98/ijsc-15-3-301.PMC9396021.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39648595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of Osteogenic Differentiation of Adipose-Derived Stromal Cells by Co-Treatment with 3, 4'-Dihydroxyflavone, U0126, and N-Acetyl Cysteine.","authors":"Kwonwoo Song,&nbsp;Gwang-Mo Yang,&nbsp;Jihae Han,&nbsp;Minchan Gil,&nbsp;Ahmed Abdal Dayem,&nbsp;Kyeongseok Kim,&nbsp;Kyung Min Lim,&nbsp;Geun-Ho Kang,&nbsp;Sejong Kim,&nbsp;Soo Bin Jang,&nbsp;Balachandar Vellingiri,&nbsp;Ssang-Goo Cho","doi":"10.15283/ijsc22044","DOIUrl":"https://doi.org/10.15283/ijsc22044","url":null,"abstract":"Background and Objectives Flavonoids form the largest group of plant phenols and have various biological and pharmacological activities. In this study, we investigated the effect of a flavonoid, 3, 4’-dihydroxyflavone (3, 4’-DHF) on osteogenic differentiation of equine adipose-derived stromal cells (eADSCs). Methods and Results Treatment of 3, 4’-DHF led to increased osteogenic differentiation of eADSCs by increasing phosphorylation of ERK and modulating Reactive Oxygen Species (ROS) generation. Although PD98059, an ERK inhibitor, suppressed osteogenic differentiation, another ERK inhibitor, U0126, apparently increased osteogenic differentiation of the 3, 4’-DHF-treated eADSCs, which may indicate that the effect of U0126 on bone morphogenetic protein signaling is involved in the regulation of 3, 4’-DHF in osteogenic differentiation of eADSCs. We revealed that 3, 4’-DHF could induce osteogenic differentiation of eADSCs by suppressing ROS generation and co-treatment of 3, 4’-DHF, U0126, and/or N-acetyl cysteine (NAC) resulted in the additive enhancement of osteogenic differentiation of eADSCs. Conclusions Our results showed that co-treatment of 3, 4’-DHF, U0126, and/or NAC cumulatively regulated osteogenesis in eADSCs, suggesting that 3, 4’-DHF, a flavonoid, can provide a novel approach to the treatment of osteoporosis and can provide potential therapeutic applications in therapeutics and regenerative medicine for human and companion animals.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/da/ae/ijsc-15-3-334.PMC9396012.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40406880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xenogeneic Humoral Immune Responses to Human Mesenchymal Stem Cells in Mice.","authors":"Jun-Man Hong,&nbsp;Jin-Hee Kim,&nbsp;Gwang-Hoon Kim,&nbsp;Hyun-Mu Shin,&nbsp;Young-Il Hwang","doi":"10.15283/ijsc21116","DOIUrl":"https://doi.org/10.15283/ijsc21116","url":null,"abstract":"<p><strong>Background and objectives: </strong>Many preclinical studies have been conducted using animal disease models to determine the effectiveness of human mesenchymal stem cells (hMSCs) for treating immune and inflammatory diseases based on the belief that hMSCs are not immunogenic across species. However, several researchers have suggested xenogeneic immune responses to hMSCs in animals, still without detailed features. This study aimed to investigate a xenogeneic humoral immune response to hMSCs in mice in detail.</p><p><strong>Methods and results: </strong>Balb/c mice were intraperitoneally injected with adipose tissue-derived or Wharton's jelly-derived hMSCs. Sera from these mice were titrated for each isotype. To confirm specificity of the antibodies, hMSCs were stained with the sera and subjected to a flow cytometic analysis. Spleens were immunostained for proliferating cell nuclear antigen to verify the germinal center formation. Additionally, splenocytes were subjected to a flow cytometric analysis for surface markers including GL-7, B220, CD4, CD8, CD44, and CD62L. Similar experiments were repeated in C57BL/6 mice. The results showed increased IgG1 and IgG2a titers in the sera from Balb/c mice injected with hMSCs, and the titers were much higher in the secondary sera than in the primary sera. These antibodies were specifically stained the hMSCs. Germinal centers were observed in the spleen, and flow cytometric analysis of the splenocytes showed higher frequencies of centroblasts (B220⁺ GL7⁺) and memory T cells (CD62L⁺ CD44⁺) both in CD4⁺ and CD8⁺ subsets. Similar results were obtained for C57BL/6 mice.</p><p><strong>Conclusions: </strong>hMSCs induced a humoral immune response in mice, with characters of T cell-dependent immunity.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8e/36/ijsc-15-3-291.PMC9396016.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39648596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-29a-3p Inhibits Proliferation and Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells via Targeting FOXO3 and Repressing Wnt/<i>β</i>-Catenin Signaling in Steroid-Associated Osteonecrosis.","authors":"Changgeng Wang,&nbsp;Minghui Zhu,&nbsp;Demeng Yang,&nbsp;Xinyuan Hu,&nbsp;Xinyuan Wen,&nbsp;Aimei Liu","doi":"10.15283/ijsc21147","DOIUrl":"https://doi.org/10.15283/ijsc21147","url":null,"abstract":"<p><strong>Background and objectives: </strong>This study was to investigate the role of microRNA-29a-3p (miR-29a-3p) in human bone marrow mesenchymal stem cells (hBMSCs), and its relationship with steroid-associated osteonecrosis.</p><p><strong>Methods and results: </strong>The online tool GEO2R was used to screen out the differentially expressed genes (DEGs) in GSE123568 dataset. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-29a-3p, forkhead box O3 (FOXO3), alkaline phosphatase (ALP), bone gamma-carboxyglutamate protein (OCN) and RUNX family transcription factor 2 (Runx2) in the hBMSCs isolated from the patients with steroid- associated osteonecrosis. CCK-8 assay was executed to measure cell viability; western blot assay was utilized to detect FOXO3, ALP, Runx2, OCN and <i>β</i>-catenin expression. Cell apoptosis and cell cycle were detected by flow cytometry. Immunofluorescence assay was used to detect the sub-cellular localization of <i>β</i>-catenin. Bioinformatics analysis and luciferase reporter gene assay were performed to confirm whether miR-29a-3p can combine with FOXO3 3'UTR. MiR-29a-3p was markedly up-regulated in the hBMSCs of patients with steroid-associated osteonecrosis, while FOXO3 mRNA was significantly down-regulated. Transfection of miR-29a-3p mimics significantly inhibited the hBMSCs' proliferation, osteogenic differentiation markers' expressions, including ALP, Runx2, OCN, and repressed the ALP activity, as well as promoted cell apoptosis and cell-cycle arrest. FOXO3 was identified as a target gene of miR-29a-3p, and miR-29a-3p can inhibit the expression of FOXO3 and <i>β</i>-catenin, and inhibition of miR-29a-3p promoted translocation of <i>β</i>-catenin to the nucleus.</p><p><strong>Conclusions: </strong>MiR-29a-3p can modulate FOXO3 expression and Wnt/<i>β</i>-catenin signaling to inhibit viability and osteogenic differentiation of hBMSCs, thereby promoting the development of steroid-associated osteonecrosis.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5f/df/ijsc-15-3-324.PMC9396013.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40409641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}