Animal models and experimental medicine最新文献

{"title":"Stem cell-based therapies for type 1 diabetes: Progress in differentiation, clinical translation, and immune protection.","authors":"Zifan Li, Yu Kang, Yuyu Niu","doi":"10.1002/ame2.70211","DOIUrl":"https://doi.org/10.1002/ame2.70211","url":null,"abstract":"<p><p>Transplantation of insulin-producing cells derived from pluripotent stem cells represents a highly promising approach for the radical treatment of type 1 diabetes (T1D). Informed by a comprehensive understanding of fetal pancreatic development, directed differentiation protocol for generating pancreatic β cells from pluripotent stem cells has been established and has achieved considerable advances, enabling the production of mature, fully functional β cells that closely recapitulate the characteristics of native pancreatic β cells. Preclinical studies have shown that the transplantation of stem cell-derived islets (SC-islets) reverses hyperglycemia in both mouse and nonhuman primate models, with a favorable safety profile. Early-phase clinical trials have further corroborated the safety and efficacy of this approach, a subset of patients with long-standing T1D achieved insulin independence, described as a \"functional cure\", with no serious adverse events of clinical significance reported. Despite these encouraging results, substantial challenges remain. With respect to differentiation protocols, insufficient functional maturity, pronounced cellular heterogeneity, significant batch-to-batch variability, and the challenges of large-scale manufacturing represent the principal unresolved limitations. Of particular concern, immune rejection remains a critical barrier even after the transplantation of autologous SC-islets, necessitating continued reliance on immunosuppressive therapy. Cell encapsulation and gene editing strategies have emerged as potential approaches to overcome this immunological barrier. In this review, we discuss strategies for obtaining insulin-producing cells from diverse cellular sources, summarize the latest advances in stem cell-based diabetes therapy, and propose future research directions.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic alcohol consumption compromises gut barrier integrity and promotes endotoxemia: Implications for sepsis susceptibility in immunocompromised hosts.","authors":"Thansita Bhunyakarnjanarat, Chatsuree Suksamai, Dhammika Leshan Wannigama, Kent Doi, Wiwat Chancharoenthana, Asada Leelahavanichkul","doi":"10.1002/ame2.70218","DOIUrl":"https://doi.org/10.1002/ame2.70218","url":null,"abstract":"<p><strong>Background: </strong>Gut barrier integrity prevents microbial translocation and systemic infection. Chronic alcohol disrupts this barrier, but its role in infection susceptibility among immune-compromised hosts remains unclear. We investigated how chronic alcohol promotes gut barrier dysfunction, endotoxemia, and dysbiosis, predisposing to bacterial translocation and sepsis.</p><p><strong>Methods: </strong>Twenty-four-week-old female FcγRIIb^-/- and wild-type mice received oral gavage of 35% ethanol (4.2 g/kg/day) or water for 10 weeks. Gut barrier integrity was assessed by serum endotoxin, FITC-dextran permeability, ileal claudin-1, and intestinal IgG/neutrophil infiltration. Systemic inflammation was evaluated by serum TNF-α, IL-1β, and IL-6; gut microbiota by 16S rRNA sequencing. Bone marrow-derived macrophages and hepatocytes from both genotypes were stimulated with LPS or ethanol to assess inflammatory responses, mitochondrial damage, and cGAS-STING activation.</p><p><strong>Results: </strong>Chronic alcohol induced gut barrier dysfunction in both groups, with more severe effects in FcγRIIb^-/- mice, which showed marked increases in serum endotoxin and FITC-dextran permeability, reduced claudin-1, and enhanced intestinal IgG deposition with neutrophil accumulation. Serum TNF-α, IL-1β, and IL-6 were significantly elevated, reflecting a sepsis-like profile. Alcohol induced dysbiosis with an increased Firmicutes-to-Bacteroidota ratio, elevated Lachnospiraceae, and reduced Alistipes, Bacteroides, and Odoribacter. In vitro, LPS elicited stronger inflammation than ethanol in both cell types, with FcγRIIb^-/- cells producing greater cytokine levels. Both stimuli caused comparable mitochondrial damage and cGAS-STING activation.</p><p><strong>Conclusions: </strong>Alcohol-induced gut barrier dysfunction, endotoxemia, and dysbiosis predispose to bacterial translocation and early sepsis, particularly in hosts with impaired inhibitory Fcγ receptor signaling, supporting gut barrier preservation as a strategy for preventing alcohol-associated infections and sepsis.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porcine kidney xenotransplantation: From primate models to clinical reality.","authors":"Zihang Guo, Ling Zhang, Shoulong Deng, Chuan Qin","doi":"10.1002/ame2.70195","DOIUrl":"https://doi.org/10.1002/ame2.70195","url":null,"abstract":"<p><p>The escalating global incidence of end-stage renal disease has exacerbated the critical shortage of kidneys from human donors. Porcine kidney xenotransplantation has emerged as the most promising alternative solution to providing an unlimited organ supply. In this review, we examine the historical evolution, current breakthroughs and future directions of kidney xenotransplantation. We probe the milestones from early attempts and non-human primate (NHP) experiments to recent clinical trials involving both brain-dead and living human recipients. The core of this review provides an in-depth discussion of the significant barriers in kidney xenotransplantation, including immune rejection, physiological incompatibilities and the risk of cross-species infection. Next, we systematically outline the multifaceted strategies developed to overcome these barriers. The rapid development of gene editing technology has enabled the establishment of multigene-edited pigs. These donors feature knockout of key carbohydrate antigen genes and expression of various human proteins, including complement regulators, anticoagulants, and immunomodulators. These genetic modifications have extended xenograft survival in NHP models to over 750 days. This is synergized with novel immunosuppressive regimens, tolerance-induction protocols, cellular therapies, and emerging adjuncts like bioengineering materials and organoid-on-a-chip technologies. Finally, we discuss future directions, raising concerns about potential complications arising from the biomechanical incompatibility between pigs and human in xenotransplantation, highlighting the need to deploy advanced multi-omics to identify unknown xenoantigens, optimize bioengineering materials for local immunomodulation, and validate extracellular vesicles as non-invasive biomarkers. While challenges for long-term xenograft survival remain, kidney xenotransplantation is rapidly advancing from preclinical research to clinical reality, holding huge potential to resolve the organ shortage crisis.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SDPR-STK38 axis controls the proliferation-differentiation balance in alveolar type II cells.","authors":"Jie Wang, Xuepei Lei, Yiying Huang, Jiaming Tang, Guiying Shi, Hang Li, Lin Bai","doi":"10.1002/ame2.70204","DOIUrl":"https://doi.org/10.1002/ame2.70204","url":null,"abstract":"<p><strong>Background: </strong>Alveolar type II (AT2) cells act as progenitors that sustain gas exchange and drive postinjury repair. Disruption of their proliferation-differentiation balance promotes pulmonary fibrosis and acute respiratory distress syndrome, but the core regulatory mechanisms are unclear. Serum deprivation response protein (SDPR, cavin-2), a caveolae-associated protein involved in proliferation and lipid metabolism, may modulate AT2 fate. This study investigated how the SDPR-STK38 axis regulates AT2 proliferation and differentiation and its impact on lung homeostasis and regeneration.</p><p><strong>Methods: </strong>SDPR knockout (SDPR^- ^/ ^-) mice and wild-type littermates were used to evaluate alveolar structure, AT2/AT1 composition, and lung function at baseline and after LPS-induced acute lung injury. Histology, immunostaining, and lung function tests were combined with mass spectrometry and co-immunoprecipitation to identify SDPR-interacting proteins. Gain- and loss-of-function assays in lung tissues and cells were used to assess how SDPR and STK38 regulate GSK-3β/cyclin D1 signaling and Notch-Hes1-dependent AT2 differentiation. Data were analyzed using standard statistical tests appropriate for the experimental design.</p><p><strong>Results: </strong>SDPR deficiency disrupted alveolar architecture and impaired lung function, accompanied by excessive AT2 expansion and reduced differentiation into AT1 cells. Proteomic and biochemical analyses identified STK38 as a novel SDPR-binding protein. SDPR loss increased STK38 expression, enhanced GSK-3β/cyclin D1 signaling, and promoted AT2 proliferation, while simultaneously reducing Hes1 expression, impairing vacuole formation, and attenuating AT2 differentiation. In the LPS model, SDPR^- ^/ ^- mice developed more severe pathological injury and declined lung function compared to wild-type controls.</p><p><strong>Conclusions: </strong>The SDPR-STK38 axis coordinately controls the proliferation-differentiation balance of AT2 cells via GSK-3β/cyclin D1 and Notch-Hes1 signaling. SDPR deficiency drives aberrant AT2 expansion, blocks differentiation toward AT1 cells, and aggravates acute lung injury, highlighting this pathway as a potential therapeutic target for promoting alveolar regeneration.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A microscopically assisted limited colectomy mouse model of early colon cancer.","authors":"Yu Han, Yixin Zhang, Dazhi Gao, Xuefeng Zhao","doi":"10.1002/ame2.70175","DOIUrl":"https://doi.org/10.1002/ame2.70175","url":null,"abstract":"<p><strong>Background: </strong>Currently, there is a lack of an adequate rodent model for investigating surgical techniques and comprehensive treatment options for patients with colorectal cancer (CRC). This study presents a mouse model that involves the orthotopic implantation of colon cancer, followed by a limited colectomy, with the aim of addressing this issue.</p><p><strong>Methods: </strong>To establish an early colon tumor model, luciferase-tagged CT-26 cells were implanted into the ascending colon wall of BALB/c mice. After a 1-week observation period, a limited colectomy procedure was performed. The progression of cancer and the impact of resection were monitored using bioluminescence imaging. Additionally, both short-term and long-term effects of surgical intervention were assessed.</p><p><strong>Results: </strong>The study demonstrated a 100% success rate (40/40) in establishing the BALB/c mouse model of early colon cancer. The technical success rate of limited colectomy was also 100%, with no instances of early mortality or morbidity. After the limited colectomy procedure, none of the animals exhibited any primary tumors, bloody ascites, recurrence or local invasion, intestinal obstruction, lymph node metastasis, peritoneal seeding, or anastomotic leakage. Furthermore, there were no reported deaths during the postresection observation period in animals treated with limited colectomy.</p><p><strong>Conclusion: </strong>In summary, our research group has successfully described a novel and reproducible surgical resection model for colon cancer in mice, which reflects the clinical scenario.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel mouse model of endometriosis: Simulating the recurrent hemorrhagic microenvironment of clinical lesions.","authors":"Yu Zhuang, Yan Zan, Tiantian Ma, Xiaoquan Huang, Junwei Li, Liangjun Xia, Yuping Sa, Youbing Xia","doi":"10.1002/ame2.70205","DOIUrl":"https://doi.org/10.1002/ame2.70205","url":null,"abstract":"<p><p>Current models of endometriosis (EMs) still have limitations in replicating the key pathological features of human EMs, particularly the cyclic bleeding associated with ectopic lesions. To address this gap, this study aimed to develop a proof-of-concept mouse model that incorporates repeated retrograde hemorrhagic exposure through the intraperitoneal injection of endometrial fragments, followed by repeated intraperitoneal injections of fresh whole blood. An EMs model was established in female C57BL/6J mice via intraperitoneal injection of endometrial fragments combined with saline or whole blood, respectively. The model was systematically evaluated using ectopic lesion burden, peritoneal adhesion scores, histopathological staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (RT-qPCR). Both models successfully recapitulated the fundamental pathological features of EMs. However, the intraperitoneal injection of whole blood (IPBI) protocol induced a markedly greater lesion burden, together with more pronounced histopathological and molecular alterations, and recapitulated repeated exposure to retrograde menstruation. In addition, the IPBI group exhibited more robust systemic biomarker responses, indicating enhanced clinical relevance. The present study successfully established a proof-of-concept EMs mouse model that introduces repeated retrograde hemorrhagic exposure to create a clinically relevant, blood-stimulated microenvironment. This model provides a reliable tool for investigating the pathogenesis of EMs and developing therapeutic strategies.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics data mining combined with experimental validation reveals ferroptosis- and autophagy-associated hub genes as diagnostic candidates and immune modulators in atherosclerosis.","authors":"Xinou Zheng, Jinling Zheng, Xuezhuang Li, Hua Chen, Li Zhang, Yuqiong Zhao, Yahao Ling","doi":"10.1002/ame2.70208","DOIUrl":"https://doi.org/10.1002/ame2.70208","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Atherosclerosis (AS) is a chronic inflammatory vascular disease that can lead to severe cardiovascular events. Ferroptosis and autophagy have been increasingly recognized for their significant roles in AS; however, few clinically translatable hub genes that connect these processes in atherosclerotic lesions have been identified. There is an urgent need for novel diagnostic and therapeutic targets to improve the early detection and intervention of AS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We downloaded AS-related datasets from the Gene Expression Omnibus (GEO) database. Common genes were identified using Limma and Weighted Gene Coexpression Network Analysis (WGCNA). We assessed ferroptosis and autophagy marker expression in AS mouse coronary tissues using immunohistochemistry (IHC) and immunofluorescence (IF). Hub genes were identified by intersecting common genes with known ferroptosis- and autophagy-related gene sets. Gene Set Enrichment Analysis (GSEA), receiver operating characteristic (ROC) curves, and 10-fold cross-validation repeated five times were performed to explore the potential roles and diagnostic capabilities of these hub genes. Immune cell infiltration analysis was performed using CIBERSORT, and Spearman's correlation analysis was subsequently performed to evaluate the associations between the identified hub genes and the relative abundance of immune cells. Finally, hub gene expression was validated in AS mouse coronary tissues using IHC and IF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Limma and WGCNA identified 104 common genes. IHC and IF analyses in AS mice confirmed the activation of ferroptosis and inhibition of autophagy in the coronary tissue. Intersecting common genes with pathway-specific genes identified three pivotal hub genes: CALCOCO2, TXNRD1, and SELENBP1. ROC analysis and 10-fold cross-validation repeated five times indicated excellent diagnostic efficacy for these genes. Immune infiltration analysis revealed significant alterations in immune cell populations in AS patients, and correlation analysis further demonstrated that CALCOCO2, TXNRD1, and SELENBP1 were significantly associated with multiple immune cell types, directly linking these hub genes to the atherosclerotic immune microenvironment. Consistent with patient data, IHC/IF validation showed significantly lower expression of the hub genes in AS mouse coronary tissues compared to controls.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;CALCOCO2, TXNRD1, and SELENBP1 represent a novel panel of diagnostic biomarkers uniquely positioned at the intersection of ferroptosis and autophagy in AS. The robust diagnostic performance of these hub genes, as demonstrated by ROC analysis and cross‑validation, was further consolidated by IHC/IF validation showing their consistently downregulated expression in AS mouse models. Furthermore, these hub genes are significantly correlated with multiple immune cell populations, directly linking them to the atherosclerotic imm","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Humanized immune system animal models and their recent applications.","authors":"Nicolas Skuli, Rudra B Amin, A'ishah Bakayoko, Marisa Kruidenier, Sahara Aqui, Sarah J Skuli, Terence P Gade","doi":"10.1002/ame2.70212","DOIUrl":"10.1002/ame2.70212","url":null,"abstract":"<p><p>Human or humanized immune system (HIS) animal models have emerged as indispensable tools for studying human biology and disease in vivo. By engrafting human hematopoietic and hematopoietic stem cells (HSC) into immunodeficient hosts, these models have enabled the development of a functional HIS, allowing the study of immune responses, disease mechanisms, and therapeutic interventions in a physiologically relevant setting. HIS models have broad applications across cancer research, infectious disease, regenerative medicine, and immunotherapy development. This review provides a comprehensive overview of the current landscape of HIS model generation, including HSC-based approaches, host strain selection, and recent advances involving genetically engineered mouse models expressing human cytokines and human leukocyte antigen molecules. We evaluated the strengths and limitations of these models, including issues with incomplete immune reconstitution and species-specific incompatibilities. We also discuss their increasing role in preclinical drug development and explore emerging innovations such as multitissue humanization and genome-editing strategies. As HIS models continue to evolve, they provide strong opportunities to bridge basic research and clinical translation.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USB1 deficiency disrupts neutrophil maturation via RNA dysregulation independent of global pre-mRNA splicing.","authors":"Hang Li, Guiying Shi, Jiaming Tang, Yiying Huang, Jie Wang, Xuepei Lei, Lin Bai","doi":"10.1002/ame2.70206","DOIUrl":"10.1002/ame2.70206","url":null,"abstract":"<p><strong>Background: </strong>U6 biogenesis 1 (USB1) gene mutations cause poikiloderma with neutropenia (PN), which is clinically characterized by skin hyperpigmentation, nail dysplasia, neutropenia, and an elevated risk of cancer. USB1 functions as an RNA exonuclease involved in RNA maturation and stability regulation, although its precise mechanism of action in the hematopoietic system remains unclear.</p><p><strong>Methods: </strong>We established a myeloid cell-specific USB1 knockout mouse model (USB1fl/fl-Lyz2-cre) using CRISPR/Cas9. Using a combination of research methods, including Western blot, flow cytometry, messenger RNA (mRNA) sequencing, microRNA (miRNA) sequencing, and quantitative polymerase chain reaction (qPCR), we investigated the effects of USB1 deficiency on neutrophil development and differentiation, along with the underlying signaling molecular mechanisms.</p><p><strong>Results: </strong>Experimental results indicated that USB1 deficiency in mouse myeloid cells not only leads to dysregulation of miRNA expression but also interferes with the developmental, differentiation, and maturation processes of neutrophils by affecting key genes, such as IL1a, Selp, and Kilt. This impact can be traced back to the stages of myeloid progenitor cells.</p><p><strong>Conclusions: </strong>USB1 influences neutrophil maturation and myeloid progenitor cell differentiation by regulating the expression of specific miRNAs and mRNAs. This provides novel in vivo experimental evidence for understanding the pathogenesis of PN in patients.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147724986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer therapy-induced ototoxicity: Current challenges and emerging management strategies.","authors":"Yuqi Huang, Baoying Xu, Xinru Chen, Yu Chen, Dehong Yu","doi":"10.1002/ame2.70201","DOIUrl":"https://doi.org/10.1002/ame2.70201","url":null,"abstract":"<p><p>Cochleovestibular impairment is a debilitating sequela of oncological intervention, resulting from multifaceted organic damage to the inner ear. Clinically manifesting as sensorineural hearing loss and vestibular dysfunction, ototoxicity significantly compromises cognitive health and long-term quality of life. Despite its prevalence, early detection and prophylactic intervention remain clinically suboptimal. This review provides a comprehensive analysis of the molecular pathogenesis and risk factors-including age, specific genetic polymorphisms, and cumulative dosage-associated with various cancer modalities such as platinum-based chemotherapy, radiotherapy, and emerging immunotherapies. We specifically evaluate the cellular mechanisms of cisplatin-induced irreversible damage to the stria vascularis and hair cells. Furthermore, this article critiques current clinical monitoring protocols, advocating for the integration of baseline audiological screening and high-frequency auditory assessments as mandatory standards of care. Finally, we synthesize the current therapeutic landscape, ranging from established otoprotective agents and cochlear implants to novel candidate drugs in the preclinical pipeline. By bridging mechanistic research with translational evidence, this review emphasizes a precision-medicine approach to balance therapeutic efficacy with the preservation of auditory integrity for cancer survivors.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}