STEM CELLS最新文献_第5页

METTL3 promotes osteogenesis by regulating N6-methyladenosine-dependent primary processing of hsa-miR-4526. METTL3通过调节n6 -甲基腺苷依赖的hsa-miR-4526初级加工促进成骨。

IF 4 2区医学

STEM CELLS Pub Date : 2025-01-04 DOI: 10.1093/stmcls/sxae089

Yidan Song, Hongyu Gao, Yihua Pan, Yuxi Gu, Wentian Sun, Jun Liu

{"title":"METTL3 promotes osteogenesis by regulating N6-methyladenosine-dependent primary processing of hsa-miR-4526.","authors":"Yidan Song, Hongyu Gao, Yihua Pan, Yuxi Gu, Wentian Sun, Jun Liu","doi":"10.1093/stmcls/sxae089","DOIUrl":"https://doi.org/10.1093/stmcls/sxae089","url":null,"abstract":"The function and mechanism of pri-miRNA N6-methyladenosine (m6A) modification in promoting miRNA maturation and regulating osteoblastic differentiation are not fully understood. The aim of this study was to investigate the role and regulatory mechanism of miRNA shear maturation regulated by methyltransferase like 3 (METTL3) in human adipose-derived stem cell (hASC) osteogenesis. Firstly, we found METTL3 promoted osteogenesis both in vivo and in vitro. Subsequently, three pri-miRNAs with the most significant methylated peaks were identified through methylated RNA immunoprecipitation sequencing (MeRIP-seq). Through quantitative real-time polymerase chain reaction (qRT-PCR), MeRIP-qPCR and co-immunoprecipitation (CO-IP), it was determined that METTL3 promoted the processing of hsa-miR-4526 by mediating pri-miR4526/5190 m6A modification. Subsequent in vivo and in vitro experiments demonstrated that hsa-miR-4526 promoted osteogenesis. Dual luciferase reporter assay was performed to verify that hsa-miR-4526 regulated osteogenic differentiation through TUBB3. It was found that TUBB3 can inhibit hASC osteogenesis. Further rescue experiments confirmed that METTL3 inhibited TUBB3 expression through hsa-miR-4526, thereby regulating osteogenic differentiation. RNA-seq revealed that TUBB3 may be involved in cell metabolism, calcium enrichment, osteoclast differentiation, and other pathways. Our study is the first to investigate the mechanism of pri-miRNA m6A modification in regulating hASC osteogenesis, presenting a novel idea and method for repairing bone defects.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enforced hematopoietic cell E-selectin/L-selectin ligand expression enhances bone marrow stromal cells homing and amelioration of cerebral ischemia-reperfusion injury via induction of prostaglandin E2. 强制 HCELL 表达可通过诱导 PGE2 增强骨髓基质细胞的归巢并改善脑缺血再灌注损伤。

IF 4 2区医学

STEM CELLS Pub Date : 2024-12-06 DOI: 10.1093/stmcls/sxae062

Lian Yi, Yewei Qu, Qi Zhang, Shanshan Shi, Fangqin Li, Changda Qu, Yushi Tang, Shirong Wen, Yujun Pan

{"title":"Enforced hematopoietic cell E-selectin/L-selectin ligand expression enhances bone marrow stromal cells homing and amelioration of cerebral ischemia-reperfusion injury via induction of prostaglandin E2.","authors":"Lian Yi, Yewei Qu, Qi Zhang, Shanshan Shi, Fangqin Li, Changda Qu, Yushi Tang, Shirong Wen, Yujun Pan","doi":"10.1093/stmcls/sxae062","DOIUrl":"10.1093/stmcls/sxae062","url":null,"abstract":"Ischemic stroke (IS) is a significant and potentially life-threatening disease with limited treatment options, often resulting in severe disability. Bone marrow stromal cells (BMSCs) transplantation has exhibited promising neuroprotection following cerebral ischemia-reperfusion injury (CIRI). However, the effectiveness is hindered by their low homing rate when administered through the vein. In this study, we aimed to enhance the homing ability of BMSCs through lentivirus transfection to express fucosyltransferase 7. This glycosylation engineered CD44 on BMSCs to express hematopoietic cell E-selectin/L-selectin ligand (HCELL), which is the most potent E-selectin ligand. Following enforced HCELL expression, the transplantation of BMSCs was then evaluated in a middle cerebral artery occlusion model. Results showed that HCELL+BMSCs significantly ameliorated neurological deficits and reduced the volume of cerebral infarction. Furthermore, the transplantation led to a decrease in apoptosis by upregulating BCL-2 and downregulating BAX, also reduced the mRNA levels of inflammatory factors, such as interleukin-1β (IL-1β), IL-2, IL-6, and tumor necrosis factor-alpha (TNF-α) in the ischemic brain tissue. Notably, enforced HCELL expression facilitated the migration of BMSCs toward cerebral ischemic lesions and their subsequent transendothelial migration through the upregulation of PTGS-2, increased production of PGE2 and activation of VLA-4. In summary, our study demonstrates that transplantation of HCELL+BMSCs effectively alleviates CIRI, and that enforced HCELL expression enhances the homing of BMSCs to cerebral ischemic lesions and their transendothelial migration via PTGS-2/PGE2/VLA-4. These findings indicate that enforced expression of HCELL on BMSCs could serve as a promising therapeutic strategy for the treatment of ischemic stroke.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1070-1084"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NLRP3 deficiency improves bone healing of tooth extraction sockets through SMAD2/3-RUNX2-mediated osteoblast differentiation. 缺乏 NLRP3 可通过 SMAD2/3-RUNX2 介导的成骨细胞分化改善拔牙窝的骨愈合。

IF 4 2区医学

STEM CELLS Pub Date : 2024-12-06 DOI: 10.1093/stmcls/sxae064

Ying Geng, Chen Bao, Yue Chen, Ziwei Yan, Fen Miao, Ting Wang, Yingyi Li, Lu Li, Wen Sun, Yan Xu

{"title":"NLRP3 deficiency improves bone healing of tooth extraction sockets through SMAD2/3-RUNX2-mediated osteoblast differentiation.","authors":"Ying Geng, Chen Bao, Yue Chen, Ziwei Yan, Fen Miao, Ting Wang, Yingyi Li, Lu Li, Wen Sun, Yan Xu","doi":"10.1093/stmcls/sxae064","DOIUrl":"10.1093/stmcls/sxae064","url":null,"abstract":"Impaired bone healing following tooth extraction poses a significant challenge for implantation. As a crucial component of the natural immune system, the NLRP3 inflammasome is one of the most extensively studied pattern-recognition receptors, and is involved in multiple diseases. Yet, the role of NLRP3 in bone healing remains to be clarified. Here, to investigate the effect of NLRP3 on bone healing, we established a maxillary first molar extraction model in wild-type and NLRP3KO mice using minimally invasive techniques. We observed that NLRP3 was activated during the bone repair phase, and its depletion enhanced socket bone formation and osteoblast differentiation. Moreover, NLRP3 inflammasome activation was found to inhibit osteogenic differentiation in alveolar bone-derived mesenchymal stem cells (aBMSCs), an effect mitigated by NLRP3 deficiency. Mechanistically, we established that the SMAD2/3-RUNX2 signaling pathway is a downstream target of NLRP3 inflammasome activation, and SMAD2/3 knockdown partially reversed the significant decrease in expression of RUNX2, OSX, and ALP induced by NLRP3. Thus, our findings demonstrate that NLRP3 negatively modulates alveolar socket bone healing and contributes to the understanding of the NLRP3-induced signaling pathways involved in osteogenesis regulation.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1085-1099"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunomodulatory potential of cytokine-licensed human bone marrow-derived mesenchymal stromal cells correlates with potency marker expression profile. 细胞因子许可的人骨髓间充质基质细胞的免疫调节潜力与效力标记表达谱相关。

IF 4 2区医学

STEM CELLS Pub Date : 2024-12-06 DOI: 10.1093/stmcls/sxae053

Jiemin Wang, Yingying Zhou, Ellen Donohoe, Aoife Canning, Seyedmohammad Moosavizadeh, Aideen E Ryan, Thomas Ritter

{"title":"Immunomodulatory potential of cytokine-licensed human bone marrow-derived mesenchymal stromal cells correlates with potency marker expression profile.","authors":"Jiemin Wang, Yingying Zhou, Ellen Donohoe, Aoife Canning, Seyedmohammad Moosavizadeh, Aideen E Ryan, Thomas Ritter","doi":"10.1093/stmcls/sxae053","DOIUrl":"10.1093/stmcls/sxae053","url":null,"abstract":"Cytokine(s) pre-activation/licensing is an effective way to enhance the immunomodulatory potency of mesenchymal stromal cells (MSCs). Currently, IFN-γ licensing received the most attention in comparison with other cytokines. After licensing human bone marrow-derived MSCs with pro-/anti-inflammatory cytokines IFN-γ, IL-1β, TNF-α, TGF-β1 alone or in combination, the in vitro immunomodulatory potency of these MSCs was studied by incubating with allogeneic T cells and macrophage-like THP-1 cells. In addition, immunomodulation-related molecules filtered by bioinformatics, complement 1 subcomponent (C1s), and interferon-induced GTP-binding protein Mx2 (MX2), were studied to verify whether to reflect the immunomodulatory potency. Herein, we reported that different cytokines cause different effects on the function of MSC. While TGF-β1 licensing enhances the capacity of MSCs to induce T cells with an immunosuppressive phenotype, IFN-γ-licensing strengthens the inhibitory effect of MSC on T cell proliferation. Both TGF-β1 and IFN-γ licensing can enhance the effect of MSC on reducing the expression of pro-inflammatory cytokines by M1 macrophage-like THP-1 cells. Interestingly, IFN-γ upregulates potential potency markers extracellular C1s and kynurenine (KYN) and intracellular MX2. These 3 molecules have the potential to reflect mesenchymal stromal cell immunomodulatory potency. In addition, we reported that there is a synergistic effect of TGF-β1 and IFN-γ in immunomodulation.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1040-1054"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metformin acts on miR-181a-5p/PAI-1 axis in stem cells providing new strategies for improving age-related osteogenic differentiation decline. 二甲双胍作用于干细胞中的 miR-181a-5p/PAI-1 轴，为改善与年龄相关的成骨分化衰退提供了新策略。

IF 4 2区医学

STEM CELLS Pub Date : 2024-12-06 DOI: 10.1093/stmcls/sxae057

Guanhao Hong, Yulan Zhou, Shukai Yang, Shouquan Yan, Jiaxu Lu, Bo Xu, Zeyu Zhan, Huasheng Jiang, Bo Wei, Jiafeng Wang

{"title":"Metformin acts on miR-181a-5p/PAI-1 axis in stem cells providing new strategies for improving age-related osteogenic differentiation decline.","authors":"Guanhao Hong, Yulan Zhou, Shukai Yang, Shouquan Yan, Jiaxu Lu, Bo Xu, Zeyu Zhan, Huasheng Jiang, Bo Wei, Jiafeng Wang","doi":"10.1093/stmcls/sxae057","DOIUrl":"10.1093/stmcls/sxae057","url":null,"abstract":"A general decline in the osteogenic differentiation capacity of human bone marrow mesenchymal stem cells (hBMSCs) in the elderly is a clinical consensus, with diverse opinions on the mechanisms. Many studies have demonstrated that metformin (MF) significantly protects against osteoporosis and reduces fracture risk. However, the exact mechanism of this effect remains unclear. In this study, we found that the decreased miR-181a-5p expression triggered by MF treatment plays a critical role in recovering the osteogenic ability of aging hBMSCs (derived from elderly individuals). Notably, the miR-181a-5p expression in hBMSCs was significantly decreased with prolonged MF (1000 μM) treatment. Further investigation revealed that miR-181a-5p overexpression markedly impairs the osteogenic ability of hBMSCs, while miR-181a-5p inhibition reveals the opposite result. We also found that miR-181a-5p could suppress the protein translation process of plasminogen activator inhibitor-1 (PAI-1), as evidenced by luciferase assays and Western blots. Additionally, low PAI-1 levels were associated with diminished osteogenic ability, whereas high levels promoted it. These findings were further validated in human umbilical cord mesenchymal stem cells (hUCMSCs). Finally, our in vivo experiment with a bone defects rat model confirmed that the agomiR-181a-5p (long-lasting miR-181a-5p mimic) undermined bone defects recovery, while the antagomiR-181a-5p (long-lasting miR-181a-5p inhibitor) significantly promoted the bone defects recovery. In conclusion, we found that MF promotes bone tissue regeneration through the miR-181a-5p/PAI-1 axis by affecting MSC osteogenic ability, providing new strategies for the treatment of age-related bone regeneration disorders.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1055-1069"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CD44: a stemness driver, regulator, and marker-all in one? CD44：集干性驱动因子、调节因子和标记因子于一身？

IF 4 2区医学

STEM CELLS Pub Date : 2024-12-06 DOI: 10.1093/stmcls/sxae060

Steffen J Sonnentag, Nagwa S M Ibrahim, Veronique Orian-Rousseau

引用次数: 0

Correction to: Combination of Systemic Chemotherapy with Local Stem Cell Delivered S-TRAIL in Resected Brain Tumors. 更正：全身化疗与局部干细胞给药 S-TRAIL 在切除脑肿瘤中的联合应用。

IF 4 2区医学

STEM CELLS Pub Date : 2024-12-06 DOI: 10.1093/stmcls/sxae059

引用次数: 0

Enforced HCELL expression: empowering "Step 1" to optimize the efficacy of mesenchymal stem/stromal cell therapy for stroke and other clinical conditions. 强制 HCELL 表达：增强 "第一步 "的能力，优化间充质干细胞/基质细胞治疗中风和其他临床疾病的疗效。

IF 4 2区医学

STEM CELLS Pub Date : 2024-12-06 DOI: 10.1093/stmcls/sxae067

Robert Sackstein

引用次数: 0

Correction: Immunomodulatory Functions of Adipose Mesenchymal Stromal/Stem Cell Derived From Donors With Type 2 Diabetes and Obesity on CD4 T Cells. 更正：来自2型糖尿病和肥胖供体的脂肪间充质基质/干细胞对CD4 T细胞的免疫调节功能。

IF 4 2区医学

STEM CELLS Pub Date : 2024-12-06 DOI: 10.1093/stmcls/sxad043

引用次数: 0

Mesenchymal stromal cell transplantation ameliorates fibrosis and microRNA dysregulation in skeletal muscle ischemia. 间充质基质细胞移植可改善骨骼肌缺血中的纤维化和微RNA失调。

IF 4 2区医学

STEM CELLS Pub Date : 2024-11-05 DOI: 10.1093/stmcls/sxae058

Clara Sanz-Nogués, Alan J Keane, Michael Creane, Sean O Hynes, Xizhe Chen, Caomhán J Lyons, Emma Horan, Stephen J Elliman, Katarzyna Goljanek-Whysall, Timothy O'Brien

{"title":"Mesenchymal stromal cell transplantation ameliorates fibrosis and microRNA dysregulation in skeletal muscle ischemia.","authors":"Clara Sanz-Nogués, Alan J Keane, Michael Creane, Sean O Hynes, Xizhe Chen, Caomhán J Lyons, Emma Horan, Stephen J Elliman, Katarzyna Goljanek-Whysall, Timothy O'Brien","doi":"10.1093/stmcls/sxae058","DOIUrl":"10.1093/stmcls/sxae058","url":null,"abstract":"Peripheral arterial disease (PAD) is associated with lower-extremity muscle wasting. Hallmark features of PAD-associated skeletal muscle pathology include loss of skeletal muscle mass, reduced strength and physical performance, increased inflammation, fibrosis, and adipocyte infiltration. At the molecular level, skeletal muscle ischemia has also been associated with gene and microRNA (miRNA) dysregulation. Mesenchymal stromal cells (MSCs) have been shown to enhance muscle regeneration and improve muscle function in various skeletal muscle injuries. This study aimed to evaluate the effects of intramuscularly delivered human umbilical cord-derived MSCs (hUC-MSCs) on skeletal muscle ischemia. Herein, we report an hUC-MSC-mediated amelioration of ischemia-induced skeletal muscle atrophy and function via enhancement of myofiber regeneration, reduction of tissue inflammation, adipocyte accumulation, and tissue fibrosis. These changes were observed in the absence of cell-mediated enhancement of blood flow recovery as measured by laser Doppler imaging. Furthermore, reduced tissue fibrosis in the hUC-MSC-treated group was associated with upregulation of miR-1, miR-133a, and miR-29b and downregulation of targeted pro-fibrotic genes such as Col1a1 and Fn1. Our results support the use of hUC-MSCs as a novel approach to reduce fibrosis and promote skeletal muscle regeneration after ischemic injury in patients with PAD.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"976-991"},"PeriodicalIF":4.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0