STEM CELLS最新文献_第8页

Stem cells within the HPA axis in tissue homeostasis and disease. HPA轴内的干细胞在组织稳态和疾病中的作用。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-08-22 DOI: 10.1093/stmcls/sxaf039

Mario Schubert, Kaomei Guan, Charlotte Steenblock

{"title":"Stem cells within the HPA axis in tissue homeostasis and disease.","authors":"Mario Schubert, Kaomei Guan, Charlotte Steenblock","doi":"10.1093/stmcls/sxaf039","DOIUrl":"10.1093/stmcls/sxaf039","url":null,"abstract":"The hypothalamus-pituitary-adrenal (HPA) axis is crucial for energy metabolism, cardiovascular function, and stress response. Importantly, neuronal signaling circuits in the hypothalamus, along with hormones released from the pituitary and adrenal gland, must adapt to physiological demands or pathological conditions. Stem and progenitor cells are pivotal in this regulation, either by giving rise to distinct cell types or by interacting with progenitor or hormone-producing cells. While lineage-tracing studies in rodent models have explored the role of stem cells in the HPA axis, our understanding of the mechanisms underlying this dynamic tissue plasticity remains limited, especially in humans. Moreover, single-cell RNA sequencing has revealed significant heterogeneity among stem cell populations in the HPA-axis, raising questions about the functional relevance of individual subclusters during development and adulthood. In this concise review, we summarize current knowledge on stem cells in the HPA axis, focusing on their origins, localization of different stem cell populations, and sex-specific activity in maintaining tissue integrity. We further address their role under pathophysiological conditions, including metabolic disease, cancer, and stress. Lastly, we discuss emerging strategies for replacing lost or damaged stem or progenitor cells during aging, highlighting recent achievements in the in vitro differentiation of hypothalamic, pituitary, and adrenal stem cells.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537603","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

Contribution of cytokeratin 19-expressing cells towards islet regeneration induced by multipotent stromal cell secreted proteins. 表达细胞角蛋白19的细胞对多能基质细胞分泌蛋白诱导胰岛再生的贡献。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-08-22 DOI: 10.1093/stmcls/sxaf036

Nazihah Rasiwala, Gillian I Bell, Anargyros Xenocostas, David A Hess

{"title":"Contribution of cytokeratin 19-expressing cells towards islet regeneration induced by multipotent stromal cell secreted proteins.","authors":"Nazihah Rasiwala, Gillian I Bell, Anargyros Xenocostas, David A Hess","doi":"10.1093/stmcls/sxaf036","DOIUrl":"10.1093/stmcls/sxaf036","url":null,"abstract":"Residual beta cell function has been documented in \"medalist\" patients who have lived with Type 1 diabetes (T1D) for >50 years. In addition, endocrine cell neogenesis first occurs in the developing human embryo from progenitor cells derived from pancreatic ductal epithelial structure. Thus, beta cell conversion from a dormant epithelial precursor remains a promising approach to regenerate islets during T1D. We have previously shown that intra-pancreatic (iPan) injection of Wnt pathway-stimulated conditioned media (Wnt+ CdM) generated from human bone marrow-derived multipotent stromal cells (MSC) contained islet regenerative factors that reduced hyperglycemia and recovered beta cell mass in streptozotocin-treated mice. However, the endogenous source of regenerated beta cells remains unknown. Herein, we employed cytokeratin 19 (CK19)-CreERT Rosa26-mTomato lineage-tracing mice to assess the endocrine conversion of CK19+ cells during MSC CdM-induced islet regeneration. Mice iPan-injected with Wnt+ CdM demonstrated reduced blood glucose levels and improved glucose tolerance compared to mice injected with unconditioned basal media. CdM-injected mice also showed increased islet number and beta cell mass, as well as CK19+ cells within regenerating islets. The frequency of insulin + cells that co-expressed tdTomato within dissociated pancreas samples observed via flow cytometry was 5-fold higher in Wnt+ CdM-injected mice (~5%) compared to basal media-injected controls (~1%). Collectively, in vivo lineage tracing revealed conversion of CK19+ cells to functional beta cells partially contributed to islet regeneration induced by Wnt-activated MSC CdM. Future studies are required to delineate alternate cell types and mechanisms participating in islet regeneration induced by direct delivery of MSC-CdM.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12371234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256928","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

A molecular systems architecture of the mesenchymal stromal cell microenvironment. 间充质间质细胞微环境的分子系统结构。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-08-22 DOI: 10.1093/stmcls/sxaf042

V A Shiva Ayyadurai, Prabhakar Deonikar, Vishvatha Radhakrishnan, Armand Keating

{"title":"A molecular systems architecture of the mesenchymal stromal cell microenvironment.","authors":"V A Shiva Ayyadurai, Prabhakar Deonikar, Vishvatha Radhakrishnan, Armand Keating","doi":"10.1093/stmcls/sxaf042","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf042","url":null,"abstract":"A systems-level understanding of immunomodulatory, regenerative, and pro-/antifibrosis functions of mesenchymal stromal cells (MSCs) is critical to advance MSCs as a viable therapeutic option. Given the complexity of MSCs and their interactions with microenvironmental cells, a systems biology approach may enable such understanding to achieve practical objectives such as target identification, combination therapeutics, clinical strategies, and avoidance of adverse effects. In this study, a molecular systems architecture of MSCs microenvironment is developed to organize the complexity of biomolecular interactions between MSCs and other microenvironmental cells. This architecture provides a visual mapping of MSC interactions, identifies the complex crosstalk between MSCs and cells in the microenvironment, reveals potential targets, and offers a framework for creating future predictive, quantitative computational (in silico) models of the MSC microenvironment. The development of combination therapeutics, clinical strategies to improve therapeutic efficacy, and avoidance of adverse effects can be facilitated by such in silico models. However, it must all begin with a molecular systems architecture of MSCs-the objective and result of this study.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":"43 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12371236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937412","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

Healthy human induced pluripotent stem cell-derived cardiomyocytes exhibit sex dimorphism even without the addition of hormones. 健康的人类诱导多能干细胞衍生的心肌细胞即使在没有添加激素的情况下也表现出性别二态性。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-08-22 DOI: 10.1093/stmcls/sxaf038

Sophie E Givens, Abygail A Andebrhan, Eric G Schmuck, Aimee Renaud, An Xie, Somayeh Ebrahimi-Barough, Juan E Abrahante, Noah Stanis, Samuel Dudley, James R Dutton, Brenda M Ogle

{"title":"Healthy human induced pluripotent stem cell-derived cardiomyocytes exhibit sex dimorphism even without the addition of hormones.","authors":"Sophie E Givens, Abygail A Andebrhan, Eric G Schmuck, Aimee Renaud, An Xie, Somayeh Ebrahimi-Barough, Juan E Abrahante, Noah Stanis, Samuel Dudley, James R Dutton, Brenda M Ogle","doi":"10.1093/stmcls/sxaf038","DOIUrl":"10.1093/stmcls/sxaf038","url":null,"abstract":"Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a valuable cell type for studying human cardiac health and disease in vitro. However, it is not known whether hiPSC-CMs display sex dimorphism and therefore whether sex should be incorporated as a biological variable in in vitro studies that include this cell type. To date, the vast majority of studies that utilize hiPSC-CMs do not include both male and female sex nor stratify results based on sex because it is challenging to amass such a cohort of cells. Here, we generated 3 female and 3 male hiPSC lines from adult left ventricular cardiac fibroblasts as a resource for studying sex differences in in vitro cardiac models. We used this resource to generate hiPSC-CMs and maintained them in basal media without exogenous hormones. Functional assessment of CMs showed enhanced calcium handling in female-derived hiPSC-CMs relative to male. Bulk RNA sequencing revealed over 300 differentially expressed genes (DEGs) between male and female hiPSC-CMs. Gene ontology analysis of DEGs showed distinct differences in pathways related to cardiac pathology including cell-cell adhesion, metabolic processes, and response to ischemic stress. Differential expression of the sodium channel auxiliary unit SCN3B was found and validated through patch-clamp measurements of sodium currents, showing increased peak amplitude and window current in female hiPSC-CMs. These findings highlight the importance of considering sex as a variable when conducting studies to evaluate aspects of human cardiac health and disease related to CM function.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12371235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511285","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

m6A mRNA demethylase FTO promotes chondrogenic differentiation of human bone marrow mesenchymal stem cells by targeting SMAD3. m6A mRNA去甲基化酶FTO通过靶向SMAD3促进人骨髓间充质干细胞成软骨分化。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-08-22 DOI: 10.1093/stmcls/sxaf035

Tao Shu, Dongfeng Zhang, Jiachun Li, Hanzhong Liu, Lukuan Cui, Juyuan Gu, Liang Wu, Wenfen Liu, Junming Wan, Xiaozuo Zheng

{"title":"m6A mRNA demethylase FTO promotes chondrogenic differentiation of human bone marrow mesenchymal stem cells by targeting SMAD3.","authors":"Tao Shu, Dongfeng Zhang, Jiachun Li, Hanzhong Liu, Lukuan Cui, Juyuan Gu, Liang Wu, Wenfen Liu, Junming Wan, Xiaozuo Zheng","doi":"10.1093/stmcls/sxaf035","DOIUrl":"10.1093/stmcls/sxaf035","url":null,"abstract":"Bone marrow mesenchymal stem cells (BMSCs) have chondrogenic differentiation potential to treat cartilage injury. N6 methyladenosine (m6A), one of the most prevalent mRNA modifications, has been reported to be crucial in cartilage disease. Herein, we further investigated the effects and underlying mechanisms in the modification of m6A on the chondrogenic differentiation of MSCs. This study showed that the m6A level was decreased in the chondrogenic differentiation of MSCs and m6A mRNA demethylation fat mass and obesity-associated protein (FTO) played an important role in these processes. The overexpression of FTO has been demonstrated to improve the levels of chondrogenic markers. We confirmed that FTO directly bound to SMAD3 mRNA and increased its demethylation, which promoted the chondrogenic differentiation of MSCs. We further indicated that the m6A \"reader\" YTHDF2 was probably related to the chondrogenic differentiation of MSCs. SiFTO attenuated the SiYTHDF2-increased mRNA stability of SMAD3, leading to the declining levels of chondrogenic markers. Collectively, these results reveal FTO could act as an important mediator of SMAD3 mRNA demethylation and improve the chondrogenic differentiation of MSCs.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504332","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

Exosomes derived from bone marrow-derived mesenchymal stem cells of exercise-trained mice improve wound healing by inhibiting macrophage M1 polarization. 运动训练小鼠骨髓间充质干细胞衍生的外泌体通过抑制巨噬细胞M1极化改善伤口愈合。

IF 4 2区医学

STEM CELLS Pub Date : 2025-07-21 DOI: 10.1093/stmcls/sxae081

Jiling Qiu, Yifan Zhao, Yingyi Chen, Yanxue Wang, Juan Du, Junji Xu, Lijia Guo, Yi Liu

{"title":"Exosomes derived from bone marrow-derived mesenchymal stem cells of exercise-trained mice improve wound healing by inhibiting macrophage M1 polarization.","authors":"Jiling Qiu, Yifan Zhao, Yingyi Chen, Yanxue Wang, Juan Du, Junji Xu, Lijia Guo, Yi Liu","doi":"10.1093/stmcls/sxae081","DOIUrl":"10.1093/stmcls/sxae081","url":null,"abstract":"Background: Engaging in appropriate exercise is advantageous for our well-being. We investigated whether exercise could affect the paracrine function of BMSCs and whether exosomes derived from treadmill exercise-trained mouse (Exo-tread) BMSCs could engender more pronounced effects on wound healing.Methods: First, the effects of treadmill exercise on mouse BMSCs biological functions, exosomes secretion quantity, and identification were assessed. Furthermore, we assessed the effects of Exo-tread on M1 macrophage by qPCR and FCM in vitro. Additionally, the expressions and phosphorylation status of p65 and p38 proteins were analyzed via Western blotting. For the in vivo component, we induced wound models of mice. Subsequently, we assessed the effects of Exo-tread using various methodologies including imaging, H&E, Masson, immunohistochemical, and immunofluorescence staining. To demonstrate whether Exo-tread could act through macrophages, we further depleted mouse macrophages.Results: Exercise accelerated the proliferation of BMSCs and the secretion of exosomes. In vitro, Exo-tread markedly decreased the expression of inflammatory factors while concurrently suppressing M1 polarization in mouse peritoneal macrophages compared with the Exo-ctrl group. These observed effects were potentially mediated by the reduction in the M1 polarization ratio, achieved through the inhibition of p65 and p38 phosphorylation. Similarly, in vivo experiments demonstrated that Exo-tread significantly enhanced wound healing by attenuating inflammatory cytokines and M1 macrophages.Conclusions: Exo-tread facilitates wound healing by mitigating the inflammatory response, achieved through a reduction in the M1 polarization ratio.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264978","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

DNA hydroxy methylases Tet1 and Tet2 regulate bone aging and bone marrow stromal cell metabolism through the IGF-1/mTOR signaling axis. DNA羟甲基化酶Tet1和Tet2通过IGF-1/ mTOR信号轴调节骨老化和BMSC代谢。

IF 4 2区医学

STEM CELLS Pub Date : 2025-07-21 DOI: 10.1093/stmcls/sxaf026

Nicholas Smith, Dimitrios Cakouros, Feargal J Ryan, David J Lynn, Sharon Paton, Agnieszka Arthur, Stan Gronthos

{"title":"DNA hydroxy methylases Tet1 and Tet2 regulate bone aging and bone marrow stromal cell metabolism through the IGF-1/mTOR signaling axis.","authors":"Nicholas Smith, Dimitrios Cakouros, Feargal J Ryan, David J Lynn, Sharon Paton, Agnieszka Arthur, Stan Gronthos","doi":"10.1093/stmcls/sxaf026","DOIUrl":"10.1093/stmcls/sxaf026","url":null,"abstract":"The Ten-Eleven Translocases (Tet) family of DNA hydroxymethylases have recently been implicated in bone development, with Tet1 and Tet2 mediating Bone Marrow Stromal Cell (BMSC) growth and osteogenic differentiation. The present study investigated the effects of Tet1 and Tet2 deregulation on bone development and age-related bone loss, with respect to BMSC function. Histomorphometric and micro-CT analysis of skeletal parameters found significant reductions to trabecular structure and volume as well as reduced osteoblast numbers within the bone of Prx1:Cre driven Tet1 and Tet2 double knockout (TetDKO) mice at skeletal maturity. Moreover, these effects were exacerbated with age, particularly in male mice. In vitro, studies found a significant reduction in TetDKO BMSC osteogenic potential and a shift towards adipogenesis, as well as changes to DNA repair, proliferation, and senescence properties. RNA sequencing of BMSC derived from TetDKO male mice uncovered several differentially expressed genes, and an array of significantly enriched gene set pathways. Notably, Pappa2, involved in the regulation of IGF-1 signaling, was significantly differentially regulated, leading to a reduction in IGF-1 bioavailability and signaling in BMSC and differentiated osteoblasts. Furthermore, changes in mTOR activity in TetDKO animals indicated altered metabolic activity, differentiation, and proliferation capabilities of TetDKO BMSC. These findings indicate that Tet1 and 2 regulate the IGF-1 regulatory element, Pappa2, where deregulation of Tet1 and Tet2 in BMSC can disrupt this pathway leading to enhanced bone loss and premature aging. Targeting these novel regulatory pathways may offer new therapeutic approaches for the treatment of age-related bone loss.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961839","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

Cerulenin partially corrects the disrupted developmental transcriptomic signature in Huntington's disease striatal medium spiny neurons. 蓝绿蛋白部分纠正亨廷顿氏病纹状体中棘神经元发育转录组特征的中断。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-07-21 DOI: 10.1093/stmcls/sxaf029

Carlos Galicia Aguirre, Kizito-Tshitoko Tshilenge, Elena Battistoni, Alejandro Lopez-Ramirez, Swati Naphade, Kevin Perez, Akos A Gerencser, Sicheng Song, Sean D Mooney, Simon Melov, Michelle E Ehrlich, Lisa M Ellerby

{"title":"Cerulenin partially corrects the disrupted developmental transcriptomic signature in Huntington's disease striatal medium spiny neurons.","authors":"Carlos Galicia Aguirre, Kizito-Tshitoko Tshilenge, Elena Battistoni, Alejandro Lopez-Ramirez, Swati Naphade, Kevin Perez, Akos A Gerencser, Sicheng Song, Sean D Mooney, Simon Melov, Michelle E Ehrlich, Lisa M Ellerby","doi":"10.1093/stmcls/sxaf029","DOIUrl":"10.1093/stmcls/sxaf029","url":null,"abstract":"Huntington's disease (HD) is a neurodegenerative disorder caused by an expansion of CAG repeats in exon 1 of the huntingtin (HTT) gene, resulting in a mutant HTT (mHTT) protein. Although mHTT is expressed in all tissues, it significantly affects medium spiny neurons (MSNs) in the striatum, resulting in their loss and the subsequent motor function impairment in HD. While HD symptoms typically emerge in midlife, disrupted MSN neurodevelopment is important. To explore the effects of mHTT on MSN development, we differentiated HD-induced pluripotent stem cells (iPSCs) and isogenic controls into neuronal stem cells, and then generated a developing MSN population encompassing early, intermediate progenitors, and nascent MSNs. Single-cell RNA sequencing revealed that the developmental trajectory of MSNs in our model closely emulated the trajectory of human fetal striatal neurons. However, in the HD MSN cultures, several crucial genes required for proper MSN maturation were downregulated, including members of the DLX family of transcription factors. Our analysis also uncovered a progressive dysregulation of multiple HD-related pathways as MSNs developed, including the NRF2-mediated oxidative stress response and mitogen-activated protein kinase signaling. Using the transcriptional profile of developing HD MSNs, we searched the L1000 dataset for small molecules that induce the opposite gene expression pattern. We pinpointed numerous small molecules with known benefits in HD models and previously untested novel molecules. A top candidate, Cerulenin, partially restored the DARPP-32 levels and electrical activity in HD MSNs, and also modulated genes involved in multiple HD-related pathways.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961537","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

Stem cell CNTF promotes olfactory epithelial neuroregeneration and functional recovery following injury. 干细胞CNTF促进嗅觉上皮神经再生和损伤后功能恢复。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-07-21 DOI: 10.1093/stmcls/sxaf033

Derek Cox, Brian Wang, Joe Oliver, Jaeden Pyburn, Diego J Rodriguez-Gil, Theo Hagg, Cuihong Jia

{"title":"Stem cell CNTF promotes olfactory epithelial neuroregeneration and functional recovery following injury.","authors":"Derek Cox, Brian Wang, Joe Oliver, Jaeden Pyburn, Diego J Rodriguez-Gil, Theo Hagg, Cuihong Jia","doi":"10.1093/stmcls/sxaf033","DOIUrl":"10.1093/stmcls/sxaf033","url":null,"abstract":"Olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) are continuously replaced by neuroregeneration from basal stem cells. Acute inflammation destroys OSNs, causing hyposmia or anosmia, but leaves the basal stem cells intact. We previously found that ciliary neurotrophic factor (CNTF) is highly expressed in horizontal basal cells (HBCs) and the CNTF receptor is in globose basal cells (GBCs), which are the actively dividing cells that normally replace dying OSNs. Here, we investigated the role of CNTF in basal stem cell proliferation/differentiation and smell function recovery following methimazole-induced acute inflammatory OE injury. Methimazole increased inflammatory markers, TNFα, IL-6, and CD45, and depleted OSNs in the OE at 3 and 5 days. Simultaneously, CNTF and the GBC marker Mash1 were upregulated, suggesting that HBCs produced more CNTF, as validated using primary HBC cultures, to promote GBC proliferation. Methimazole increased GBC proliferation, as shown by the number of BrdU-labeled GBCs in CNTF+/+, but not in CNTF-/- littermate mice. Also, CNTF+/+ mice had higher levels of neuroregeneration and better smell function recovery than CNTF-/- littermates. This indicates that CNTF promotes GBC proliferation and promotes OE neuroregeneration and smell functional recovery. This study identifies the regenerative role of CNTF in HBCs and reveals the therapeutic potential to target CNTF signaling to improve olfactory neuroregeneration and functional recovery following injury.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118493","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

Neural stem cell-derived extracellular vesicles alleviate inflammatory responses in a mouse model of atopic dermatitis. 神经干细胞来源的细胞外囊泡减轻了特应性皮炎小鼠模型的炎症反应。

IF 4 2区医学

STEM CELLS Pub Date : 2025-07-21 DOI: 10.1093/stmcls/sxaf034

Seulbee Lee, Donghun Hyun, Yong Namkung, Boram Park, Byounggwan Lee, Junhyung Myung, Sunghoi Hong

{"title":"Neural stem cell-derived extracellular vesicles alleviate inflammatory responses in a mouse model of atopic dermatitis.","authors":"Seulbee Lee, Donghun Hyun, Yong Namkung, Boram Park, Byounggwan Lee, Junhyung Myung, Sunghoi Hong","doi":"10.1093/stmcls/sxaf034","DOIUrl":"10.1093/stmcls/sxaf034","url":null,"abstract":"Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by disrupted epidermal barrier function and excessive immune activation. Conventional treatments using corticosteroids and immunosuppressants provide only temporary relief and often induce adverse side effects, highlighting the need for novel, effective therapy. In this study, we investigated the therapeutic potential of neural stem cell-derived extracellular vesicles (NSC-EVs) derived from NSC-derived conditioned medium (NSC-CM) in modulating inflammatory responses in AD. In vitro experiments using human keratinocytes (HaCaT) and murine macrophages (RAW264.7) showed that both NSC-CM and NSC-EVs can significantly decrease the expression of proinflammatory cytokines and chemokines, inhibit the phosphorylation of NF-κB, and reduce inducible nitric oxide synthase. In addition, topical application of NSC-CM and NSC-EVs alleviated atopic symptoms, reduced mast cell infiltration, and improved skin barrier integrity in a 2,4-dinitrochlorobenzene-induced AD mouse model. Proteomic analysis identified key proteins related to immune regulation and extracellular matrix remodeling in NSC-EVs, indicating their active role in mitigating inflammation and tissue repair. Altogether, our results demonstrated the potent anti-inflammatory effects of NSC-EVs, highlighting their potential to be a novel and effective therapeutic option for AD and other inflammation-related diseases.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179789","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