STEM CELLS最新文献_第4页

Valproic acid-expanded cord blood CD34+CD90+ cells are functionally distinct based on their origin. 丙戊酸扩增的脐带血CD34+CD90+细胞根据其来源在功能上是不同的。

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-02-23 DOI: 10.1093/stmcls/sxaf079

Al Rabee Kassis, Amudha Ganapathy, Amal Mechaal, Seungwon An, John G Quigley, Dolores Mahmud, Nadim Mahmud

{"title":"Valproic acid-expanded cord blood CD34+CD90+ cells are functionally distinct based on their origin.","authors":"Al Rabee Kassis, Amudha Ganapathy, Amal Mechaal, Seungwon An, John G Quigley, Dolores Mahmud, Nadim Mahmud","doi":"10.1093/stmcls/sxaf079","DOIUrl":"10.1093/stmcls/sxaf079","url":null,"abstract":"Hematopoietic stem cell (HSC) transplantation is a potentially curative option for patients with hematologic malignancies, but donor shortages impact graft availability. Umbilical cord blood (UCB) is a viable alternative source of HSC; however, the limited numbers present in a single unit have spurred efforts to expand HSC ex vivo. We previously demonstrated that the addition of valproic acid (VPA), an anti-convulsive drug, to CB cell cultures promotes maintenance of functional HSC, but not expansion. However, it has been proposed that VPA primarily induces mitochondrial reprogramming of mature CD34+CD90- cells to more primitive CD34+CD90+ cells, rather than the replication of CD34+CD90+ cells in culture. To determine which fraction of the CD34+CD90+ cells present after culture in VPA were derived from CD34+CD90- vs. CD34+CD90+ cells, we examined the functionality of CD34+CD90+ cells derived from each flow cytometry-sorted population. During culture in VPA there was a significant increase in CD34+CD90+ cell number; the majority arising from pre-existing CD34+CD90+ cells, with minimal contribution from CD34+CD90- cells. Colony-forming unit (CFU) assays revealed reduced plating efficiency and xeno-transplantation studies demonstrated diminished in vivo hematopoietic reconstitution potential of CD34+CD90+ cells derived from relatively committed CD34+CD90- cells. Our findings indicate that while VPA supports CD34+CD90+ cell expansion, the CD34+CD90+ cells derived from CD34+CD90- cells are functionally more differentiated than those derived directly from CD34+CD90+ cells, with increased mitochondrial mass and membrane potential, but reduced regenerative potential. These results emphasize the need for functional assessments of culture-expanded HSCs to accurately determine their therapeutic potential.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751417","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

Stem cell therapy for osteoradionecrosis of the jaws: mechanisms, advances, and clinical potential. 干细胞治疗颌骨放射性骨坏死：机制、进展和临床潜力。

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-02-23 DOI: 10.1093/stmcls/sxaf078

Haiou Liu, Ran Nie, Jinlan Jiang, Congxiao Zhang

{"title":"Stem cell therapy for osteoradionecrosis of the jaws: mechanisms, advances, and clinical potential.","authors":"Haiou Liu, Ran Nie, Jinlan Jiang, Congxiao Zhang","doi":"10.1093/stmcls/sxaf078","DOIUrl":"10.1093/stmcls/sxaf078","url":null,"abstract":"Osteoradionecrosis of the jaws (ORNJ) is a severe aseptic complication of high-dose radiotherapy for head-and-neck cancers, characterized by chronic jawbone necrosis, functional impairment, and poor responses to traditional treatments (eg, hyperbaric oxygen and surgical resection) that fail to address its root pathophysiology (microcirculatory impairment, bone metabolism dysfunction). Its incidence is 1.2%-40% in patients receiving >60 Gy radiotherapy, especially with concurrent trauma. In recent years, stem cell therapy has garnered attention as a potential treatment for a variety of bone-related disorders, including the repair of bone defects, treatment of osteoarthritis, and mitigation of osteoporosis. Evidence from preclinical studies indicates that local transplantation of mesenchymal stem cells in rodent models of ORNJ significantly increases bone volume and bone mineral density. The therapeutic efficacy is primarily attributed to the cells' capacity for multidirectional differentiation, paracrine signaling, and immunomodulatory functions, highlighting their substantial potential for clinical translation. This narrative review synthesizes studies on stem cell therapy for ORNJ published from 2004 to 2024 (PubMed, Medline, Cochrane), with a focus on original research published in the most recent decade (2014-2024) to reflect the latest advances. This review consolidates ORNJ pathogenesis and stem cell mechanisms, identifies research gaps, and guides future efforts to standardize protocols and advance clinical translation.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751462","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

ETV2-ECSCR-mTOR pathways regulate reprogramming to the endothelial lineage. ETV2-ECSCR-mTOR通路调节内皮细胞谱系的重编程。

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-02-23 DOI: 10.1093/stmcls/sxaf075

Young Geun Choi, Satyabrata Das, Thijs A Larson, Anh Quynh Le, Usha Nagarajan, Hesham A Sadek, Jianyi Jay Zhang, Mary G Garry, Daniel J Garry

{"title":"ETV2-ECSCR-mTOR pathways regulate reprogramming to the endothelial lineage.","authors":"Young Geun Choi, Satyabrata Das, Thijs A Larson, Anh Quynh Le, Usha Nagarajan, Hesham A Sadek, Jianyi Jay Zhang, Mary G Garry, Daniel J Garry","doi":"10.1093/stmcls/sxaf075","DOIUrl":"10.1093/stmcls/sxaf075","url":null,"abstract":"ETV2 is a pioneer factor that regulates cell fate decisions and direct reprogramming of the endothelial lineage. While ETV2 drives the cell fate conversion through epigenetic remodeling, its downstream targets also contribute to ETV2-mediated cell fate conversion. In this study, we defined Ecscr as a direct transcriptional target of ETV2 and a key regulator of ETV2-mediated cell reprogramming. Single-cell RNA sequencing analyses of ETV2-overexpressing embryoid body differentiation and embryonic fibroblast reprogramming revealed upregulation of Ecscr in ETV2-induced cell populations. ATAC-seq, ChIP-seq, gel shift, and transcriptional assays confirmed ETV2 binding to the Ecscr gene. In vivo analyses using 3.9 kb-Etv2-EYFP reporter transgenic mice and Etv2 null mice, in combination with single-cell RNA-seq of developing mouse embryos, further validated Ecscr as an ETV2 downstream target. Functionally, the knockdown of Ecscr significantly enhanced reprogramming rate, suggesting that Ecscr functions in a feedback mechanism to decrease the ETV2-mediated cell fate conversion. Mechanistically, Ecscr knockdown led to upregulation of Rptor, a core component of mTORC1 complex. The inhibition of mTORC1 signaling with rapamycin partially reversed the effect, supporting the notion that mTORC1 functions as a downstream mediator. Our findings uncover a novel ETV2 downstream target ECSCR that modulates ETV2-driven reprogramming through mTORC1 regulation, offering a target to improve endothelial reprogramming for regenerative applications.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13017831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130398","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

Chemotherapy resistance of urinary bladder cancer mediated by a Notch and Wnt co-regulatory module of stemness. Notch和Wnt干细胞共调控模块介导的膀胱癌化疗耐药。

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-02-23 DOI: 10.1093/stmcls/sxag002

Li-Hsin Cheng, Che-Wei Hsu, Pei-Ming Yang, Tai-Yan Liao, Fang-Chi Liu, Wan-Wen Chen, Chin-Chen Pan, Chung-Chi Hsu, Kuan-Chou Chen, Kelvin K Tsai

{"title":"Chemotherapy resistance of urinary bladder cancer mediated by a Notch and Wnt co-regulatory module of stemness.","authors":"Li-Hsin Cheng, Che-Wei Hsu, Pei-Ming Yang, Tai-Yan Liao, Fang-Chi Liu, Wan-Wen Chen, Chin-Chen Pan, Chung-Chi Hsu, Kuan-Chou Chen, Kelvin K Tsai","doi":"10.1093/stmcls/sxag002","DOIUrl":"10.1093/stmcls/sxag002","url":null,"abstract":"Despite breakthroughs in molecularly targeted and immune therapies, the prognosis for patients with urinary bladder cancer (UBC) has remained unsatisfactory over the past few decades. Understanding the molecular underpinnings of UBC treatment refractoriness is crucial for identifying novel therapeutic targets and strategies. Cancer stemness plays a pivotal role in the oncogenesis and treatment resistance of UBC, while the underlying molecular regulatory mechanisms are poorly understood. We identified isoform 1 of ASPM (ASPM-i1) as the most upregulated stemness-associated factor in tumorigenic UBC cells, predominantly expressed by ALDH1+ stem-like cancer cells. Pairing genetic ASPM-i1 inhibition with standard chemotherapeutic agents used in the treatment of UBC, including cisplatin and gemcitabine, circumvents the treatment resistance of tumorigenic and stem-like UBC cells. Mechanistically, ASPM-i1 interacts with the Disheveled (DVL) and intracellular NOTCH proteins, thereby attenuating CUL3- or FBXW7-mediated ubiquitination and the subsequent proteasomal degradation. The regulatory module concomitantly enhances the activities and ligand responsiveness of the Wnt and Notch signaling pathways in UBC cells. As a result, ASPM-i1 inhibition sensitized tumorigenic UBC cells to chemotherapy in a NOTCH- and DVL-dependent manner. In human UBC tissues, ASPM-i1 shows substantial cell-to-cell heterogeneity and is upregulated in a subset (46.4%) of tumors, correlating with poor clinical prognosis. This study reveals a crucial co-regulatory module of Notch and Wnt signaling that mediates stemness and chemotherapy resistance in tumorigenic UBC cells; its inhibition provides a novel approach to enhance chemosensitivity and improve therapeutic outcomes in human UBC.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948194","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

Unveiling the gut-pancreas axis: microbial influence on stemness and tumor microenvironment of PDAC. 揭示肠胰轴：微生物对PDAC干性和肿瘤微环境的影响。

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-01-29 DOI: 10.1093/stmcls/sxaf064

Kirtana Arikath, Surinder K Batra, Moorthy P Ponnusamy

引用次数: 0

Critical insights into umbilical cord blood and tissue stem cells: navigating challenges to enhance clinical translation-a narrative review. 关键见解脐带血和组织干细胞：导航挑战，以加强临床翻译-叙述性回顾。

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-01-29 DOI: 10.1093/stmcls/sxaf077

Kosar Fateh, Amir Atashi

{"title":"Critical insights into umbilical cord blood and tissue stem cells: navigating challenges to enhance clinical translation-a narrative review.","authors":"Kosar Fateh, Amir Atashi","doi":"10.1093/stmcls/sxaf077","DOIUrl":"10.1093/stmcls/sxaf077","url":null,"abstract":"Background: Umbilical cord blood (UCB) and umbilical cord tissue (UCT) are non-invasive, readily available sources of stem cells with significant potential for regenerative medicine and hematopoietic transplantation. While hematopoietic stem cells from UCB and mesenchymal stem cells from both UCB and UCT are clinically applied, other cord-derived populations remain under investigation, offering novel therapeutic opportunities alongside translational challenges.Main body: This review synthesizes current knowledge on stem cell populations derived from UCB and UCT. Hematopoietic and mesenchymal stem cells have established clinical roles, whereas unrestricted somatic stem cells, embryonic-like stem cells, MUSE cells, and multipotent progenitor cells show preclinical promise. These populations differ in differentiation potential, therapeutic application, and biological characteristics. Translational barriers include limited cell numbers, variable engraftment, immune compatibility, and challenges in long-term preservation. Emerging strategies, such as ex vivo expansion, co-transplantation, and nanoparticle-assisted delivery, aim to enhance efficacy, precision, and safety.Conclusion: This narrative review highlights both opportunities and challenges of umbilical cord stem cell therapies. Standardized protocols, interdisciplinary collaboration, and continued innovation are essential to optimize clinical outcomes and fully realize the translational potential of these diverse populations.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145706734","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

Age-associated T cell immunity decreases circulating endothelial progenitor cells. 年龄相关的T细胞免疫减少循环内皮祖细胞。

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-01-29 DOI: 10.1093/stmcls/sxaf069

Fang Zhang, Qiuchen Zhao, Shuzhen Guo, Gen Hamanaka, Dong-Bin Back, Shin Ishikane, Ester Licastro, Ji-Hyun Park, Wenlu Li, Elga Esposito, Ksenia V Kastanenka, Brian J Bacskai, Kazuhide Hayakawa

{"title":"Age-associated T cell immunity decreases circulating endothelial progenitor cells.","authors":"Fang Zhang, Qiuchen Zhao, Shuzhen Guo, Gen Hamanaka, Dong-Bin Back, Shin Ishikane, Ester Licastro, Ji-Hyun Park, Wenlu Li, Elga Esposito, Ksenia V Kastanenka, Brian J Bacskai, Kazuhide Hayakawa","doi":"10.1093/stmcls/sxaf069","DOIUrl":"10.1093/stmcls/sxaf069","url":null,"abstract":"A reduction in circulating endothelial progenitor cells (EPCs) comprise an important part of vascular aging. However, the underlying mechanisms that mediate this EPC decline remain unclear. Here, we demonstrate a novel molecular mechanism where aging increases inhibitory T cell subsets and impairs SDF1-mediated increase of circulating EPCs. SomaScan proteomics and western blot analysis revealed FABP4 as the top upregulated protein in plasma and was also increased in the bone marrow in aging. Importantly, treatment with FABP4 in bone marrow cells increased inhibitory T cells while decreased SDF-1 receptor, CXCR4 in EPCs, whereas blocking FABP4 signaling by BMS309403 or depleting these T cells restored surface expression of CXCR4 in EPCs. Notably, FABP4-mediated decrease of circulating EPC in aging were restored by therapeutic administration of mitochondria, wherein plasma FABP4 was decreased along with reducing inhibitory T cell induction in bone marrow and increasing circulating EPCs in older mice. Collectively, these findings provide new insight into the involvement of age-associated T cell immunity in EPC dysregulation, and FABP4 may be a therapeutic target to detain vascular aging.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353417","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

Macrophage heterogeneity and plasticity in liver injury and repair mechanisms. 巨噬细胞在肝损伤和修复机制中的异质性和可塑性。

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-01-29 DOI: 10.1093/stmcls/sxaf072

Tianjiao Zhang, Paul Horn, Moritz Peiseler, Frank Tacke

{"title":"Macrophage heterogeneity and plasticity in liver injury and repair mechanisms.","authors":"Tianjiao Zhang, Paul Horn, Moritz Peiseler, Frank Tacke","doi":"10.1093/stmcls/sxaf072","DOIUrl":"10.1093/stmcls/sxaf072","url":null,"abstract":"Hepatic macrophages, encompassing embryonic Kupffer cells (emKCs) and monocyte-derived macrophages (MoMFs), are recognized as important regulators of hepatic homeostasis and key players in the pathogenesis of liver diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD). Emerging research focuses on the critical role of hepatic macrophages in mediating liver repair and regeneration following injury, where they closely interact with hepatocytes as well as hepatic stellate cells (HSCs) to regulate inflammation, fibrosis, tissue remodeling, and regeneration. The latest single-cell and spatial omics technologies have profoundly deepened our understanding of the hepatic immune response, revealing the remarkable phenotypic and spatial heterogeneity of macrophages, including distinct subsets such as lipid-associated macrophages (LAMs) within steatotic and fibrotic regions. Macrophage subsets sense systemic (e.g. gut-liver axis, adipose tissue) and local stress signals and orchestrate disease-defining cellular responses in hepatocytes, HSC, and other immune cells. Dynamic tools such as intravital microscopy have further unveiled functional properties in the spatial context hitherto unknown. Herein, we review the multifaceted roles of hepatic macrophages in liver injury and repair, with an emphasis on their role in steatosis, inflammation, fibrosis, and regeneration. We also discuss how these insights may inform the development of novel macrophage-targeted therapeutic interventions.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145501334","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

Stem cell specification and niche formation in developing incisor require actomyosin forces. 切牙发育过程中干细胞的分化和生态位的形成需要肌动球蛋白的作用。

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-01-29 DOI: 10.1093/stmcls/sxaf074

Yasmin Mohtadi Hamadani, Laura Evers, Satu-Marja Myllymäki, Emma Juuri, Maria Jussila, Paul Gueguen, Mina Mina, Irma Thesleff, Anamaria Balic

{"title":"Stem cell specification and niche formation in developing incisor require actomyosin forces.","authors":"Yasmin Mohtadi Hamadani, Laura Evers, Satu-Marja Myllymäki, Emma Juuri, Maria Jussila, Paul Gueguen, Mina Mina, Irma Thesleff, Anamaria Balic","doi":"10.1093/stmcls/sxaf074","DOIUrl":"10.1093/stmcls/sxaf074","url":null,"abstract":"Background: The precise timing of stem cell specification and niche formation during murine incisor development is poorly understood, and it is unclear whether these processes occur simultaneously or in a sequential manner. Functional dental epithelial stem cells are marked by the expression of Sox2, a transcription factor that is broadly expressed in the dental epithelium at the dentition onset and restricted to stem cells in fully developed incisor.Methods: Using genetic lineage tracing in Sox2CreERT2/+; R26RmT/mG and Sox2CreERT2/+; R26RtdT/+ embryos along with a single-cell RNA sequencing at different stages of incisor development, we investigated the timing of the stem cell specification and its temporal relationship with niche formation.Results: Our results reveal the presence of a Sox2-expressing stem cell-like population prior to formation of the functional niche. These cells localize to the leading edge of the advancing incisor epithelium where they are maintained in an undifferentiated state. Our data demonstrate presence of actomyosin network and a generation of a contractile tension, which helps confine Sox2+ stem cells to the leading edge.Conclusion: This mechanical confinement likely plays an important role in maintaining their stemness until the niche is functionally and structurally established. Partial or complete disruption of the actomyosin network disables the clustering of Sox2-expressing cells, potentially triggering their premature differentiation, and ultimately leads to impaired formation of the functional stem cell niche and abnormal growth of the incisor.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12855154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145627268","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

Catechin promotes osteogenic differentiation via AMPK-mediated autophagy activation in bone marrow mesenchymal stem cells. 儿茶素通过ampk介导的骨髓间充质干细胞自噬激活促进成骨分化。

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-01-29 DOI: 10.1093/stmcls/sxaf076

Haixia Liu, Ang Li, Jing Yue, Zhen Guo, Nian Zhou, Hang Yuan, Lijun Han, Yi Han, Guotao Peng, Yuanzhi Xu, Fuping Wen, Yiming Zhang

{"title":"Catechin promotes osteogenic differentiation via AMPK-mediated autophagy activation in bone marrow mesenchymal stem cells.","authors":"Haixia Liu, Ang Li, Jing Yue, Zhen Guo, Nian Zhou, Hang Yuan, Lijun Han, Yi Han, Guotao Peng, Yuanzhi Xu, Fuping Wen, Yiming Zhang","doi":"10.1093/stmcls/sxaf076","DOIUrl":"10.1093/stmcls/sxaf076","url":null,"abstract":"Background: Catechin (CH) exhibits protective effects on bone metabolism, but its underlying mechanism remains incompletely understood.Methods: We investigated the osteogenic effects of CH and its molecular pathways using bone marrow mesenchymal stem cells and MC-3T3-E1 preosteoblasts. Cell viability was assessed after CH treatment (1-100 μg/mL). Osteogenic differentiation was evaluated by ALP activity, mineralization, and the expression of key markers (Runx2, Opn, Ocn, Sp7). Mechanistic studies involved examining autophagy markers (LC3-II, P62) and the AMPK pathway, using pharmacological inhibitors (compound C for AMPK; 3-methyladenine for autophagy). The protective role of CH under oxidative stress was tested in hydrogen peroxide-treated cells by measuring viability, ROS levels, NRF2 translocation, and osteogenic capacity.Results: CH showed no significant cytotoxicity up to 100 μg/mL. At 10 μg/mL, it significantly enhanced osteogenic differentiation, increasing alkaline phosphatase activity (ALP), mineralization, and the gene/protein levels of osteogenic markers. CH activated autophagy (elevated LC3-II, decreased P62) and the AMPK pathway. Inhibition of AMPK or autophagy partially suppressed CH-induced osteogenesis, which was significantly rescued by CH co-treatment. Under oxidative stress, CH improved cell viability, reduced intracellular ROS, inhibited NRF2 nuclear translocation, and restored osteogenic differentiation.Conclusion: CH promotes osteogenesis primarily via the AMPK-autophagy axis and reverses oxidative stress-induced suppression of osteogenic differentiation through ROS clearance. These findings highlight its therapeutic potential for bone regeneration and related disorders.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145779670","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