Frontiers in Cell and Developmental Biology最新文献

{"title":"Potential role of SIRT1 in cell ferroptosis.","authors":"Yueming Zhang, Fanxiao Kong, Nan Li, Lina Tao, Jinghui Zhai, Jie Ma, Sixi Zhang","doi":"10.3389/fcell.2025.1525294","DOIUrl":"10.3389/fcell.2025.1525294","url":null,"abstract":"<p><p>Ferroptosis is a novel form of cell death that uniquely requires iron and is characterized by iron accumulation, the generation of free radicals leading to oxidative stress, and the formation of lipid peroxides, which distinguish it from other forms of cell death. The regulation of ferroptosis is extremely complex and is closely associated with a spectrum of diseases. Sirtuin 1 (SIRT1), a NAD + -dependent histone deacetylase, has emerged as a pivotal epigenetic regulator with the potential to regulate ferroptosis through a wide array of genes intricately associated with lipid metabolism, iron homeostasis, glutathione biosynthesis, and redox homeostasis. This review provides a comprehensive overview of the specific mechanisms by which SIRT1 regulates ferroptosis and explores its potential therapeutic value in the context of multiple disease pathologies, highlighting the significance of SIRT1-mediated ferroptosis in treatment strategies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1525294"},"PeriodicalIF":4.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11919884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New evidence for T-cadherin in COVID-19 pathogenesis, endothelial dysfunction, and lung fibrosis.","authors":"Ekaterina Semina, Vladimir Popov, Nikita Khabibullin, Polina Klimovich, Veronika Sysoeva, Ella Kurilina, Zoya Tsokolaeva, Vsevolod Tkachuk, Kseniya Rubina","doi":"10.3389/fcell.2025.1476329","DOIUrl":"10.3389/fcell.2025.1476329","url":null,"abstract":"<p><p>The COVID-19 pandemic had an unprecedented impact on all aspects of human activity worldwide, frequently resulting in post-acute sequelae and affecting multiple organ systems. The underlying mechanisms driving both acute and post-acute manifestations of COVID-19 are still poorly understood, warranting further investigation for new targets. The study represents the first attempt to explore the role of T-cadherin in COVID-19 pathogenesis as well as its implications in pulmonary fibrosis and endothelial dysfunction. First, we revealed a significant decrease in T-cadherin expression in post-mortem lung samples from COVID-19 patients. This downregulated T-cadherin expression correlated with the elevated levels of VE-cadherin and reduced levels of β-catenin, suggesting a disruption in endothelial cell-cell contact integrity and function. Second, the reciprocal relation of T-cadherin and VE-cadherin expression was further confirmed using cultured human endothelial Ea.hy926 cells. T-cadherin overexpression caused a decrease in VE-cadherin mRNA expression in cultured endothelial cells providing additional evidence in favor of their interplay. Third, employing <i>Cdh13</i> ^-/- mice, we unveiled the protective role of T-cadherin deficiency against bleomycin-induced lung fibrosis. Fourth, we demonstrated the mice lacking T-cadherin to have downregulated reactive oxygen species production and Nox2 mRNA expression in an angiotensin II-mediated endothelial dysfunction model. Our findings provide rationale for further studies into T-cadherin-mediated mechanisms in these processes.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1476329"},"PeriodicalIF":4.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitoregulin, a tiny protein at the crossroads of mitochondrial functioning, stress, and disease.","authors":"Petr Sergiev, Olga Averina, Julia Golubeva, Mikhail Vyssokikh, Olga Dontsova","doi":"10.3389/fcell.2025.1545359","DOIUrl":"10.3389/fcell.2025.1545359","url":null,"abstract":"<p><p>Mitoregulin (Mtln) is a small mitochondrial protein that was only recently identified. Despite this, a substantial number of studies on its function have already been published. Although sometimes contradictory, these studies have revealed the localization of Mtln, its protein and lipid partners, and its role in lipid homeostasis, energy metabolism, oxidative stress, and other aspects of mitochondrial functioning. Moreover, research using knockout and transgenic mouse models has revealed the important role of Mtln in mammalian physiology. Metabolic changes, along with muscle, kidney, and fat-related phenotypes, have been linked to Mtln dysfunction. In this review, we summarize a comprehensive set of published data on Mtln. While controversies remain, we seek to offer a unified view of its functions, spanning molecular mechanisms to organism-level effects.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1545359"},"PeriodicalIF":4.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress on small extracellular vesicles in diabetic nephropathy.","authors":"Bingqing Yu, Lanfeng Wang, Yiping Mao, Xinyi Hu, Yukang Lu, Jiahui He, Xiaoying Yuan, Man Zhang, Zhiping Chen","doi":"10.3389/fcell.2025.1535249","DOIUrl":"10.3389/fcell.2025.1535249","url":null,"abstract":"<p><p>Virtually all cell types are capable of secreting small extracellular vesicles (sEV), which can be internalized by recipient cells, thereby serving as vehicles for intercellular communication. The cargoes of these vesicles, such as microRNAs, circular RNAs, proteins, and lipids, play significant roles in both normal cellular functions and the pathogenesis of various diseases. Diabetic Nephropathy (DN), a complication arising from diabetes, is expected to contribute to a 54% increase in the global diabetic population between 2015 and 2030, leading to substantial economic burdens on individuals and healthcare systems. sEVs, as promising biomarkers, demonstrate diverse mechanistic responses in different types of Diabetic Kidney Disease (DKD). They also hold advantages in the early prediction of renal damage. This article reviews the functional mechanisms of sEVs in DKD and their potential as therapeutic targets and biomarkers.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1535249"},"PeriodicalIF":4.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pax1a-EphrinB2a pathway in the first pharyngeal pouch controls hyomandibular plate formation by promoting chondrocyte formation in zebrafish.","authors":"Haewon Jeon, Sil Jin, Jihyeon Kim, Saehoon Joo, Chong Pyo Choe","doi":"10.3389/fcell.2025.1482906","DOIUrl":"10.3389/fcell.2025.1482906","url":null,"abstract":"<p><p>The hyomandibular (HM) cartilage securing the lower jaw to the neurocranium in fish is a craniofacial skeletal element whose shape and function have changed dramatically in vertebrate evolution, yet the genetic mechanisms shaping this cartilage are less understood. Using mutants and rescue experiments in zebrafish, we reveal a previously unappreciated role of Pax1a in the anterior HM plate formation through EphrinB2a. During craniofacial development, <i>pax1a</i> is expressed in the pharyngeal endoderm from the pharyngeal segmentation stage to chondrocyte formation. Loss of <i>pax1a</i> leads to defects in the first pouch and to the absence of chondrocytes in the anterior region of the HM plate caused by increased cell death in differentiating osteochondral progenitors. In <i>pax1</i> mutants, a forced expression of <i>pax1a</i> by the heat shock before pouch formation rescues the defects in the first pouch and HM plate together, whereas a forced expression of <i>pax1a</i> after pouch formation rescues only the defects in the HM plate without rescuing the first pouch defects. In <i>pax1a</i> mutants, <i>ephrinb2a</i> expressed in the first pouch is downregulated when adjacent osteochondral progenitors differentiate into the chondrocytes, with mutations in <i>ephrinb2a</i> causing hyomandibular plate defects. Lastly, <i>pax1</i> mutants rescue the anterior hyomandibular plate defects by pouch-specific restoration of EphrinB2a or a heat-shock-treated expression of <i>ephrinb2a</i> after pouch formation. We propose that the Pax1a-EphrinB2a pathway in the first pouch is directly required to shape the HM plate in addition to the early role of Pax1a in the first pouch formation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1482906"},"PeriodicalIF":4.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11919851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes in cartilage microenvironment regulation and cartilage repair.","authors":"Han Longfei, Hou Wenyuan, Fang Weihua, Peng Peng, Lu Sun, Lin Kun, He Mincong, Yang Fan, He Wei, Wei Qiushi","doi":"10.3389/fcell.2025.1460416","DOIUrl":"10.3389/fcell.2025.1460416","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a debilitating disease that predominantly impacts the hip, hand, and knee joints. Its pathology is defined by the progressive degradation of articular cartilage, formation of bone spurs, and synovial inflammation, resulting in pain, joint function limitations, and substantial societal and familial burdens. Current treatment strategies primarily target pain alleviation, yet improved interventions addressing the underlying disease pathology are scarce. Recently, exosomes have emerged as a subject of growing interest in OA therapy. Numerous studies have investigated exosomes to offer promising therapeutic approaches for OA through diverse <i>in vivo</i> and <i>in vitro</i> models, elucidating the mechanisms by which exosomes from various cell sources modulate the cartilage microenvironment and promote cartilage repair. Preclinical investigations have demonstrated the regulatory effects of exosomes originating from human cells, including mesenchymal stem cells (MSC), synovial fibroblasts, chondrocytes, macrophages, and exosomes derived from Chinese herbal medicines, on the modulation of the cartilage microenvironment and cartilage repair through diverse signaling pathways. Additionally, therapeutic mechanisms encompass cartilage inflammation, degradation of the cartilage matrix, proliferation and migration of chondrocytes, autophagy, apoptosis, and mitigation of oxidative stress. An increasing number of exosome carrier scaffolds are under development. Our review adopts a multidimensional approach to enhance comprehension of the pivotal therapeutic functions exerted by exosomes sourced from diverse cell types in OA. Ultimately, our aim is to pinpoint therapeutic targets capable of regulating the cartilage microenvironment and facilitating cartilage repair in OA.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1460416"},"PeriodicalIF":4.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11919854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The BBS/CCT chaperonin complex ensures the localization of the adhesion G protein-coupled receptor ADGRV1 to the base of primary cilia.","authors":"Joshua Linnert, Deva Krupakar Kusuluri, Baran E Güler, Sarita Rani Patnaik, Helen Louise May-Simera, Uwe Wolfrum","doi":"10.3389/fcell.2025.1520723","DOIUrl":"10.3389/fcell.2025.1520723","url":null,"abstract":"<p><p>Primary cilia are antenna-like sensory organelles present on almost all eukaryotic cells. Their sensory capacity relies on receptors, in particular G-protein-coupled receptors (GPCRs) which localize to the ciliary membrane. Here we show that ADGRV1, a member of the GPCR subfamily of adhesion GPCRs, is part of a large protein network, interacting with numerous proteins of a comprehensive ciliary proteome. ADGRV1 is localized to the base of prototypic primary cilia in cultured cells and the modified primary cilia of retinal photoreceptors, where it interacts with TRiC/CCT chaperonins and the Bardet Biedl syndrome (BBS) chaperonin-like proteins. Knockdown of ADGRV1, CCT2 and 3, and BBS6 result in common ciliogenesis phenotypes, namely reduced ciliated cells combined with shorter primary cilia. In addition, the localization of ADGRV1 to primary cilia depends on the activity of a co-complex of TRiC/CCT chaperonins and the BBS chaperonin-like proteins. In the absence of components of the TRiC/CCT-BBS chaperonin co-complex, ADGRV1 is depleted from the base of the primary cilium and degraded via the proteasome. Defects in the TRiC/CCT-BBS chaperonin may lead to an overload of proteasomal degradation processes and imbalanced proteostasis. Dysfunction or absence of ADGRV1 from primary cilia may underly the pathophysiology of human Usher syndrome type 2 and epilepsy caused by mutations in <i>ADGRV1</i>.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1520723"},"PeriodicalIF":4.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic regulation of reprogramming and pluripotency: insights from histone modifications and their implications for cancer stem cell therapies.","authors":"Woori Bae, Eun A Ra, Myon Hee Lee","doi":"10.3389/fcell.2025.1559183","DOIUrl":"10.3389/fcell.2025.1559183","url":null,"abstract":"<p><p>Pluripotent stem cells (PSCs) possess the extraordinary capability to differentiate into a variety of cell types. This capability is tightly regulated by epigenetic mechanisms, particularly histone modifications. Moreover, the reprogramming of somatic or fate-committed cells into induced pluripotent stem cells (iPSCs) largely relies on these modifications, such as histone methylation and acetylation of histones. While extensive research has been conducted utilizing mouse models, the significance of histone modifications in human iPSCs is gaining increasing recognition. Recent studies underscore the importance of epigenetic regulators in both the reprogramming process and the regulation of cancer stem cells (CSCs), which are pivotal in tumor initiation and the development of treatment resistance. This review elucidates the dynamic alterations in histone modifications that impact reprogramming and emphasizes the necessity for a balance between activating and repressive marks. These epigenetic marks are influenced by enzymes such as DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). Furthermore, this review explores therapeutic strategies aimed at targeting these epigenetic modifications to enhance treatment efficacy in cancer while advancing the understanding of pluripotency and reprogramming. Despite promising developments in the creation of inhibitors for histone-modifying enzymes, challenges such as selectivity and therapy resistance continue to pose significant hurdles. Therefore, future endeavors must prioritize biomarker-driven approaches and gene-editing technologies to optimize the efficacy of epigenetic therapies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1559183"},"PeriodicalIF":4.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanism on autophagy associated cardiovascular dysfunction in <i>Drosophila melanogaster</i>.","authors":"Wei Zhang, Rong Zhou, Xinjuan Lei, Mofei Wang, Qinchun Duan, Yuanlin Miao, Tingting Zhang, Xinjie Li, Zhang Zutong, Liyang Wang, Odell D Jones, Mengmeng Xu, Joseph Bryant, Jianjie Ma, Yingli Liu, Xuehong Xu","doi":"10.3389/fcell.2025.1512341","DOIUrl":"10.3389/fcell.2025.1512341","url":null,"abstract":"&lt;p&gt;&lt;p&gt;As a highly conserved cellular process, autophagy has been the focus of extensive research due to its critical role in maintaining cellular homeostasis and its implications in cardiovascular pathogenesis. The decline in muscular function, along with the neuronal system, and increased sensitivity to stress have been recognized in multiple animal models. Autophagic defects in cardiovascular architecture and cellular dysfunction have been linked to both physiological and pathological conditions of the heart in mammals and &lt;i&gt;Drosophila&lt;/i&gt;. In this review, we systematically analyze the autophagy-associated pathways in the hearts of fruit flies and aim to provide a comprehensive understanding for developing potential treatments for patients and effective strategies for agricultural applications. This analysis elucidates the molecular mechanisms of autophagy in cardiovascular function under both physiological and pathological conditions in &lt;i&gt;Drosophila&lt;/i&gt;, offering significant insights into the development of cardiovascular diseases. The loss of key autophagy-associated proteins, including the transmembrane protein Atg9 and its partners Atg2 or Atg18, along with DmSestrin, leads to cardiac hypertrophy and structural abnormalities in &lt;i&gt;Drosophila&lt;/i&gt;, resembling the age-dependent deterioration of cardiac function. Members of the autophagy-related (Atg) gene family, cellular or nuclear skeletal lamins, and the mechanistic or mammalian target of rapamycin (mTOR) signaling pathways are critically influential in heart function in &lt;i&gt;Drosophila&lt;/i&gt;, with autophagy activation shown to suppress cardiac laminopathy. The mTORC1/C2 complexes, along with axis of Atg2-AMPK/Sirt1/PGC-1α pathway, are essential in the hearts of both mammals and fruit flies, governing cardiac development, growth, maturation, and the maintenance of cardiac homeostasis. The beneficial effects of several interventions that enhance cardiac function, including exercise and cold stress, can influence autophagy-dependent TOR activity of the serine/threonine protein kinase signaling in both mammals and &lt;i&gt;Drosophila&lt;/i&gt;. Exercise has been shown to increase autophagy when it is deficient and to inhibit it when it is excessive, highlighting the dual role of autophagy in cardiac health. This review evaluates the functional significance of autophagy in the heart, particularly in the context of &lt;i&gt;Drosophila&lt;/i&gt;, in relation to mTORC-associated autophagy and the axis of Atg2-AMPK/Sirt1/PGC-1α pathways. It systematically contrasts the molecular mechanisms underlying autophagy-related cardiovascular physiological and pathological conditions in both fruit flies and mammals. The evolutionary conservation of autophagy underscores the value of &lt;i&gt;Drosophila&lt;/i&gt; as a model for understanding broader mechanisms of autophagy across species. This study not only deepens our understanding of autophagy's role in cardiovascular function but also provides a theoretical foundation for the potential applic","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1512341"},"PeriodicalIF":4.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeat-dose toxicity of human umbilical cord mesenchymal stem cells via subcutaneous injection in NOG mice.","authors":"Lijuan Xia, Jinjin Shao, Qian Yang, Chengda Zhang, Zhiqi Xie, Linying Wang, Cong Xu, Siming Zhang, Jing Liu, Fang Liu, Yuhua Shi, Liqiang Gu, Xiaobo Lin, Jiahong Wang, Ying Chen, Yunxiang Chen, Xin Pan, Feifei Wu, Ruolang Pan, Jinfeng Liang, Lijiang Zhang","doi":"10.3389/fcell.2025.1558310","DOIUrl":"10.3389/fcell.2025.1558310","url":null,"abstract":"<p><strong>Background: </strong>Stem cell therapy shows promise for treating skin diseases and enhancing medical aesthetics. However, safety data for subcutaneous injection of stem cells remain limited. In this study, we evaluated the toxicity of human umbilical cord mesenchymal stem cells (hUC-MSCs) in NOD. Cg-Prkdc^scidIL2rg^tm1Sug/JicCrl (NOG) mice.</p><p><strong>Methods: </strong>Mice received subcutaneous hUC-MSC injections at doses of 2.5 × 10⁷ and 2.0 × 10⁸ cells/kg on days 1, 8, 12, 16, and 20, followed by withdrawal and observation for 6 weeks. Toxicity was assessed through clinical observation, behavioral analysis, pathology, organ weight measurements, and histopathology. hUC-MSC distribution was determined via validated quantitative (q)PCR and colonization was assessed using immunohistochemistry.</p><p><strong>Results: </strong>No abnormal effects on clinical responses, body weight, or food intake were observed following five repeated hUC-MSCs administrations, except for masses at the administration site in the high-dose group. Mouse activity levels increased in both dose groups 6 h post-final injection. Foamy cells were observed under the pleural membrane in high-dose mice. hUC-MSCs primarily colonized and were distributed within skin tissues 24 h after the last administration.</p><p><strong>Conclusion: </strong>The no-observed-adverse-effect level for subcutaneous hUC-MSC administration in NOG mice over 3 weeks was 2.5 × 10⁷ cells/kg. Our results will help in advancing the clinical use of hUC-MSCs, particularly for treating conditions such as atopic dermatitis.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1558310"},"PeriodicalIF":4.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}