STEM CELLS最新文献_第7页

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

The glucocorticoid receptor elicited proliferative response in human erythropoiesis is BCL11A-dependent. 糖皮质激素受体诱导的人类红细胞增殖反应依赖于 BCL11A。

IF 4 2区医学

STEM CELLS Pub Date : 2024-11-05 DOI: 10.1093/stmcls/sxae049

Maria Mazzarini, Jennifer Cherone, Truong Nguyen, Fabrizio Martelli, Lilian Varricchio, Alister P W Funnell, Thalia Papayannopoulou, Anna Rita Migliaccio

{"title":"The glucocorticoid receptor elicited proliferative response in human erythropoiesis is BCL11A-dependent.","authors":"Maria Mazzarini, Jennifer Cherone, Truong Nguyen, Fabrizio Martelli, Lilian Varricchio, Alister P W Funnell, Thalia Papayannopoulou, Anna Rita Migliaccio","doi":"10.1093/stmcls/sxae049","DOIUrl":"10.1093/stmcls/sxae049","url":null,"abstract":"Prior evidence indicates that the erythroid cellular response to glucocorticoids (GC) has developmental specificity, namely, that developmentally more advanced cells that are undergoing or have undergone fetal to adult globin switching are more responsive to GC-induced expansion. To investigate the molecular underpinnings of this, we focused on the major developmental globin regulator BCL11A. We compared: (1) levels of expression and nuclear content of BCL11A in adult erythroid cells upon GC stimulation; (2) response to GC of CD34+ cells from patients with BCL11A microdeletions and reduced BCL11A expression, and; (3) response to GC of 2 cellular models (HUDEP-2 and adult CD34+ cells) before and after reduction of BCL11A expression by shRNA. We observed that: (1) GC-expanded erythroid cells from a large cohort of blood donors displayed amplified expression and nuclear accumulation of BCL11A; (2) CD34 + cells from BCL11A microdeletion patients generated fewer erythroid cells when cultured with GC compared to their parents, while the erythroid expansion of the patients was similar to that of their parents in cultures without GC, and; (3) adult CD34+ cells and HUDEP-2 cells with shRNA-depleted expression of BCL11A exhibit reduced expansion in response to GC. In addition, RNA-seq profiling of shRNA-BCL11A CD34+ cells cultured with and without GC was similar (very few differentially expressed genes), while GC-specific responses (differential expression of GILZ and of numerous additional genes) were observed only in control cells with unperturbed BCL11A expression. These data indicate that BCL11A is an important participant in certain aspects of the stress pathway sustained by GC.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1006-1022"},"PeriodicalIF":4.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896299","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

A p21 reporter iPSC line for evaluating CRISPR-Cas9 and vector-induced stress responses. 用于评估 CRISPR-Cas9 和载体诱导的应激反应的 p21 报告 iPSC 系。

IF 4 2区医学

STEM CELLS Pub Date : 2024-11-05 DOI: 10.1093/stmcls/sxae056

Yi-Dan Sun, Guo-Hua Li, Feng Zhang, Tao Cheng, Jian-Ping Zhang, Xiao-Bing Zhang

{"title":"A p21 reporter iPSC line for evaluating CRISPR-Cas9 and vector-induced stress responses.","authors":"Yi-Dan Sun, Guo-Hua Li, Feng Zhang, Tao Cheng, Jian-Ping Zhang, Xiao-Bing Zhang","doi":"10.1093/stmcls/sxae056","DOIUrl":"10.1093/stmcls/sxae056","url":null,"abstract":"CRISPR-Cas9 editing triggers activation of the TP53-p21 pathway, but the impacts of different editing components and delivery methods have not been fully explored. In this study, we introduce a p21-mNeonGreen reporter iPSC line to monitor TP53-p21 pathway activation. This reporter enables dynamic tracking of p21 expression via flow cytometry, revealing a strong correlation between p21 expression and indel frequencies, and highlighting its utility in guide RNA screening. Our findings show that p21 activation is significantly more pronounced with double-stranded oligodeoxynucleotides (ODNs) or adeno-associated viral vectors (AAVs) compared to their single-stranded counterparts. Lentiviral vectors (LVs) and integrase-defective lentiviral vectors induce notably lower p21 expression than AAVs, suggesting their suitability for gene therapy in sensitive cells such as hematopoietic stem cells or immune cells. Additionally, specific viral promoters like SFFV significantly amplify p21 activation, emphasizing the critical role of promoter selection in vector development. Thus, the p21-mNeonGreen reporter iPSC line is a valuable tool for assessing the potential adverse effects of gene editing methodologies and vectors. Highlights Established a p21-mNeonGreen reporter iPSC line to track activation of the TP53-p21 pathway. Found a direct correlation between p21-mNeonGreen expression and indel frequencies, aiding in gRNA screening. Showed that LVs are preferable over AAVs for certain cells due to lower p21 activation, with viral promoter choice impacting p21 response.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"992-1005"},"PeriodicalIF":4.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277715","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

Correction to: High-Mobility Group At-Hook 1 Mediates the Role of Nuclear Factor I/X in Osteogenic Differentiation Through Activating Canonical Wnt Signaling. Correction to：高流动性基团 At-Hook 1 通过激活经典 Wnt 信号在成骨分化过程中调节核因子 I/X 的作用

IF 4 2区医学

STEM CELLS Pub Date : 2024-11-05 DOI: 10.1093/stmcls/sxae061

引用次数: 0

Derivation of dental epithelial-like cells from murine embryonic stem cells for tooth regeneration. 从小鼠胚胎干细胞中衍生出用于牙齿再生的牙上皮样细胞。

IF 4 2区医学

STEM CELLS Pub Date : 2024-11-05 DOI: 10.1093/stmcls/sxae052

Hong Hu, Yifan Zhao, Ce Shan, Huancheng Fu, Jinglei Cai, Zhonghan Li

{"title":"Derivation of dental epithelial-like cells from murine embryonic stem cells for tooth regeneration.","authors":"Hong Hu, Yifan Zhao, Ce Shan, Huancheng Fu, Jinglei Cai, Zhonghan Li","doi":"10.1093/stmcls/sxae052","DOIUrl":"10.1093/stmcls/sxae052","url":null,"abstract":"Teeth are comprised of epithelial and mesenchymal cells, and regenerative teeth rely on the regeneration of both cell types. Transcription factors play a pivotal role in cell fate determination. In this study, we establish fluorescence models based on transcription factors to monitor and analyze dental epithelial cells. Using Pitx2-P2A-copGFP mice, we observe that Pitx2+ epithelial cells, when combined with E14.5 dental mesenchymal cells, are sufficient for the reconstitution of teeth. Induced-Pitx2+ cells, directly isolated from the embryoid body that employs the Pitx2-GFP embryonic stem cell line, exhibit the capacity to differentiate into ameloblasts and develop into teeth when combined with dental mesenchymal cells. The regenerated teeth exhibit a complete structure, including dental pulp, dentin, enamel, and periodontal ligaments. Subsequent exploration via RNA-seq reveals that induced-Pitx2+ cells exhibit enrichment in genes associated with FGF receptors and WNT ligands compared with induced-Pitx2- cells. Our results indicate that both primary Pitx2+ and induced Pitx2+ cells possess the capability to differentiate into enamel-secreting ameloblasts and grow into teeth when combined with dental mesenchymal cells.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"945-956"},"PeriodicalIF":4.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034678","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