In vivo最新文献

{"title":"Gene Expression of <i>TGF-β1</i>, Matrix Metalloproteinases, and Collagen in Keloid Patients and Their Growth Patterns in 2D and 3D Cell Cultures: An <i>In Vitro</i> Study.","authors":"Alexander Helmer, Johann Kern, Petra Prohaska, Haneen Sadick, Benedikt Kramer, Lena Zaubitzer, Angela Schell, Nicole Rotter, Daniel Häussler","doi":"10.21873/invivo.14417","DOIUrl":"10.21873/invivo.14417","url":null,"abstract":"<p><strong>Background/aim: </strong>Keloids result from abnormal wound healing and are characterized by excess fibroblast activity, extracellular matrix (ECM) accumulation, and elevated collagen types. The contemporary research often relies on 2D cell cultures, which do not fully replicate keloid pathophysiology. Spheroid models offer a promising alternative. This study analyzed gene expression differences in keloid and normal skin tissues, evaluated mRNA expression from 2D cultures, and assessed spheroid viability as proof of concept.</p><p><strong>Materials and methods: </strong>Keloid and normal skin samples were collected from patients with auricular keloids. The tissues underwent histological and immunohistochemical analyses, RNA extraction for RT-qPCR, and 2D and 3D cell culture. Spheroids were cultivated for 21 days and analyzed for morphology, viability, and histological staining.</p><p><strong>Results: </strong>Histological analysis revealed mixed results, with higher mRNA levels of <i>COL1A1, COL3A1, TGF-β</i>1, and <i>TGF-βR1</i> in the keloids. In the 2D cultures, normal skin showed elevated <i>MMP-1, MMP-3</i>, and <i>TGF-β1</i> expression. The keloid spheroids demonstrated comparable morphology, but decreased viability after 21 days.</p><p><strong>Conclusion: </strong>Keloid gene and protein expression patterns varied among native tissue, 2D cultures, and 3D cultures. Keloid-derived spheroids displayed distinct histomorphological features compared with normal skin spheroids, suggesting that they may serve as more physiologically relevant models for future keloid research.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 5","pages":"2620-2634"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postoperative Swallowing Function After Minimally Invasive Esophagectomy Assessed by Videofluoroscopic Swallowing Study and Cough Test.","authors":"Shugo Kono, Tsutomu Kumamoto, Yuki Uchiyama, Kazuki Eimoto, Yoshinori Ishida, Yasunori Kurahashi, Tatsuro Nakamura, Yudai Hojo, Norihiko Kodama, Yoshitaka Oku, Kazuhisa Domen, Hisashi Shinohara","doi":"10.21873/invivo.14440","DOIUrl":"10.21873/invivo.14440","url":null,"abstract":"<p><strong>Background/aim: </strong>Postoperative dysphagia is a common and clinically important complication after esophagectomy; however, perioperative changes in swallowing function and airway-protective reflexes have not been well characterized. Here, we aimed to evaluate perioperative changes in swallowing function and airway-protective reflexes after minimally invasive esophagectomy with cervical esophagogastric anastomosis.</p><p><strong>Patients and methods: </strong>This prospective observational study included 20 patients who underwent minimally invasive esophagectomy between March 2023 and October 2024 at Hyogo Medical University. Swallowing physiology was assessed using videofluoroscopic swallowing studies performed preoperatively and before discharge. Cough reflex sensitivity was evaluated using a citric acid cough test as a complementary assessment of airway protection. Perioperative changes were analyzed descriptively using paired comparisons.</p><p><strong>Results: </strong>Among 18 patients with complete data, three postoperative parameters showed postoperative deterioration: hyoid bone movement (<i>p</i>=0.013), pharyngeal transit time (<i>p</i>=0.041), and the Penetration-Aspiration Scale score (<i>p</i>=0.017). The perioperative cough latency remained relatively stable (<i>p</i>=0.131). Postoperative swallowing parameters and cough latency did not show clear differences between patients with and without aspiration pneumonia.</p><p><strong>Conclusion: </strong>This study demonstrated measurable postoperative impairment in swallowing physiology after minimally invasive esophagectomy, whereas perioperative cough reflex sensitivity remained relatively stable. These findings underscore the clinical value of detailed swallowing assessment and may inform future postoperative swallowing rehabilitation strategies.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 5","pages":"2908-2918"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infection-related and Hepatobiliary Death Outcome Reports Involving Avacopan in the Japanese Pharmacovigilance Database.","authors":"Naohito Ide, Ken-Ichi Sako, Tomoji Maeda","doi":"10.21873/invivo.14441","DOIUrl":"10.21873/invivo.14441","url":null,"abstract":"<p><strong>Background/aim: </strong>Avacopan is used to treat antineutrophil cytoplasmic antibody-associated vasculitis. In Japan, serious hepatobiliary adverse events, including vanishing bile duct syndrome, have recently become a major safety concern. This study characterized reports with death recorded as the outcome involving avacopan in the Japanese Adverse Drug Event Report database (JADER).</p><p><strong>Patients and methods: </strong>Reports involving avacopan as a suspected drug and death recorded as the outcome were extracted from JADER. Adverse events were classified by primary system organ class and preferred term. Quarterly reporting trends and time-to-onset were evaluated for hepatobiliary and infection-related adverse events.</p><p><strong>Results: </strong>A total of 79 reports were identified; 64 involved patients aged ≥70 years. Infections and infestations were the most frequent system organ classes among adverse events with death recorded as the outcome (n=46), followed by hepatobiliary disorders (n=21). Vanishing bile duct syndrome was the most frequent hepatobiliary preferred term (n=13). <i>Pneumocystis jirovecii</i> pneumonia and pneumonia were the most frequent infection-related preferred terms (n=9 each). Median time-to-onset was 49 days for hepatobiliary disorders and 75 days for infections and infestations. The proportions of events occurring within 90 days were 94.1% for hepatobiliary disorders and 57.1% for infections and infestations.</p><p><strong>Conclusion: </strong>In JADER, death outcome reports involving avacopan frequently included infection-related and hepatobiliary events. Hepatobiliary events occurred mainly within 90 days, whereas infection-related events showed a broader time-to-onset distribution. These findings suggest the need for early hepatobiliary monitoring and continued attention to serious infections during avacopan treatment.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 5","pages":"2919-2926"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Beginner's Guide to the Annex E Scoring System of ISO 10993-6.","authors":"Mike Barbeck, Ole Jung, Tadas Korzinskas","doi":"10.21873/invivo.14416","DOIUrl":"10.21873/invivo.14416","url":null,"abstract":"<p><p>ISO 10993-6 provides the normative framework for assessing local tissue effects after implantation of medical device materials and is widely used in preclinical biological evaluation. Despite its broad application, the standard is frequently misunderstood in both teaching and practice, particularly regarding the logic of its semi-quantitative scoring system. This article aims to clarify the role of ISO 10993-6 within the broader ISO 10993 series, to correct a common misconception about the Annex E calculation, and to distinguish normative requirements from regulatory expectations and laboratory best practice. The Annex E irritation score is based on a weighted comparison of average test and control responses, not on an unweighted sum of raw observations. Inflammatory cell parameters and necrosis carry greater weight than neovascularization, fibrosis and fatty infiltrate. Appropriate control article selection, clinically justified time points and expert pathological interpretation are integral to valid study conduct. The ordinal nature of the scale limits arithmetic precision, and interobserver variability must be addressed through calibration and structured training. Modern implant categories, including degradable materials, porous scaffolds and combination products, may require supplementary methods beyond the standard score sheet. ISO 10993-6 remains a scientifically sound and regulatorily important tool for local biocompatibility assessment when applied with appropriate study design, experienced pathology review and transparent reporting. Training programmes should emphasize the comparative and weighted nature of the scoring system, the boundaries of normative requirements, and the need to integrate Annex E findings within the broader biological evaluation framework.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 5","pages":"2604-2619"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of S-1 Monotherapy for Salivary Duct Carcinoma With <i>MYC</i> Amplification.","authors":"Hirotaka Suto, Miyuki Kawamura, Mitsunori Morita, Hideki Sakai, Takuma Onoe, Kyoko Ikeuchi, Naoko Maeda, Koji Matsumoto","doi":"10.21873/invivo.14464","DOIUrl":"10.21873/invivo.14464","url":null,"abstract":"<p><strong>Background/aim: </strong>Salivary duct carcinoma (SDC) is a rare, highly aggressive subtype of salivary gland carcinoma, commonly characterized by overexpression of erb-b2 receptor tyrosine kinase 2 [ERBB2, commonly known as human epidermal growth factor receptor 2 (HER2)] and androgen receptor positivity. Anti-HER2 therapy, platinum-based chemotherapy, and androgen-deprivation therapy (ADT) are commonly provided as standard systemic treatments for advanced SDC; however, effective therapeutic options after failure of these treatments remain limited. The clinical efficacy of S-1 monotherapy in SDC and its predictive biomarkers are not well established. Herein, we present a case in which S-1 monotherapy showed efficacy in a case of SDC after resistance to anti-HER2 therapy, platinum-based chemotherapy, and ADT.</p><p><strong>Case report: </strong>The patient was a 70-year-old man diagnosed with HER2-positive and androgen receptor-positive SDC of the submandibular gland, who presented with multiple lung metastases. He initially received trastuzumab plus docetaxel as first-line therapy, followed by platinum-based chemotherapy and ADT, but experienced disease progression after each treatment. Comprehensive genomic profiling revealed amplifications of <i>ERBB2</i> and MYC proto-oncogene bHLH transcription factor (<i>MYC</i>). S-1 monotherapy was started as a late-line therapy. Computed tomography scans 2 months later showed shrinkage of lung and liver metastases, with disease control maintained for more than 5 months.</p><p><strong>Conclusion: </strong>S-1 monotherapy may represent a treatment option for patients with advanced SDC refractory to anti-HER2 therapy, platinum-based chemotherapy, and ADT, particularly in cases harboring <i>MYC</i> amplification.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 5","pages":"3173-3180"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissociated FoxP3 Up-regulation With Functional Surface Marker Loss Defines a Convergent Treg Paradox Across Immunological Archetypes of IgA Nephropathy and IgA Vasculitis.","authors":"Pu-Jun Fang, Ping-Hsuan Kuo, Jeng-Wei Lu, Yi-Jung Ho, Ann Chen, Shuk-Man Ka, Huang Yu Hsuan, Wun-Long Jheng, Feng-Cheng Liu","doi":"10.21873/invivo.14468","DOIUrl":"10.21873/invivo.14468","url":null,"abstract":"<p><strong>Background/aim: </strong>Immunoglobulin A nephropathy (IgAN) and immunoglobulin A vasculitis (IgAV) exhibit remarkable clinical heterogeneity, yet its underlying immunological diversity remains poorly characterized. We investigated whether high-dimensional peripheral blood immunophenotyping could identify distinct immunological archetypes and shared regulatory T cell (Treg) dysregulation across the clinical spectrum of IgAN and IgAV.</p><p><strong>Patients and methods: </strong>Four patients with biopsy-proven IgAN or clinically confirmed IgAV were prospectively enrolled. Serial multicolor flow cytometry characterized T-cell subsets, Treg populations, and B-cell subpopulations relative to healthy controls.</p><p><strong>Results: </strong>Individual-level profiling revealed four distinct immunological archetypes: activated T-cell, B-cell dominant, severe dysregulator, and quiescent each correlating with a specific clinical trajectory from decade-long stability to fatal outcome. Cross-case analysis revealed a convergent Treg paradox across all archetypes, characterized by increased intracellular forkhead box protein P3 (FoxP3) expression concurrent with depletion of key functional surface markers, including cluster of differentiation 25 (CD25), L-selectin (CD62L), and cluster of differentiation 127 (CD127). This paradox was consistently observed across all four archetypes regardless of disease severity or treatment status.</p><p><strong>Conclusion: </strong>IgAN and IgAV are not uniform immunological entities. The Treg Paradox, a dissociation between regulatory commitment and functional capacity may represent a shared pathogenic feature across clinically diverse phenotypes, warranting further validation as a potential basis for immunotype-guided precision therapy.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 5","pages":"3212-3223"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiological Profiles of Suspected Postoperative Pneumonia After Esophagectomy: A Focus on Gram-negative Pathogens.","authors":"Takeshi Matsubara, Hiroki Okamura, Kana Fujihara, Kento Nakajima, Yuto Yasuda, Koki Kawakami, Yuriko Yamada, Kazunari Ishitobi, Shunsuke Kaji, Takahito Taniura, Takayuki Tanaka, Tetsu Yamamoto, Masaaki Hidaka","doi":"10.21873/invivo.14457","DOIUrl":"10.21873/invivo.14457","url":null,"abstract":"<p><strong>Background/aim: </strong>Postoperative pneumonia is an important complication after esophagectomy for esophageal cancer. Although sputum cultures are often obtained when pneumonia is suspected, the microbiological profiles detected in this setting remain insufficiently characterized. This study aimed to describe sputum culture findings at suspected postoperative pneumonia onset, focusing on Gram-negative organisms and targetable pathogens relevant to antimicrobial selection.</p><p><strong>Patients and methods: </strong>We retrospectively reviewed 150 consecutive patients who underwent esophagectomy for esophageal cancer between January 2014 and April 2026. Patients were classified into early video-assisted thoracoscopic (VATS) esophagectomy, robot-assisted minimally invasive esophagectomy (RAMIE), and late VATS esophagectomy groups. Clinically relevant postoperative pneumonia was defined as Clavien-Dindo grade II or higher pneumonia within 30 days after surgery. Sputum cultures obtained at suspected pneumonia onset were reviewed.</p><p><strong>Results: </strong>A significantly higher incidence of pneumonia was observed in the RAMIE group (44.4%) compared to the early (19.0%) and late (24.2%) VATS groups (<i>p</i>=0.008). Sputum cultures were positive in all 44 pneumonia cases, and 60 organisms were detected. Gram-negative organisms accounted for 41 isolates (68.3%), and at least one Gram-negative organism was detected in 36 patients (81.8%). Targetable pathogens were detected in 33 patients (75.0%). No clear surgical-era-specific microbiological profile was identified among pneumonia cases.</p><p><strong>Conclusion: </strong>Sputum cultures, after esophagectomy, obtained at suspected postoperative pneumonia onset frequently revealed Gram-negative organisms and targetable pathogens. These findings provide a clinical basis for empirical antimicrobial selection and subsequent de-escalation strategies, but detected organisms should be interpreted as organism distribution rather than definitive causative pathogens.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 5","pages":"3086-3097"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does Radiographic Union Matter? Clinical Outcomes After Anterior Odontoid Screw Fixation in Elderly Patients.","authors":"Richard Zaccaria, Kenny Hagar, Olga Budarova, Dominic Simon, Bernd Wegener, Wolfgang Böcker, Eduardo Suero","doi":"10.21873/invivo.14439","DOIUrl":"10.21873/invivo.14439","url":null,"abstract":"<p><strong>Background/aim: </strong>Type II odontoid fractures in elderly patients are associated with high rates of nonunion and substantial morbidity. However, the clinical relevance of radiographic nonunion following anterior odontoid screw fixation remains unclear. This study aimed to evaluate long-term functional outcomes and health-related quality of life, with particular focus on the impact of fracture healing.</p><p><strong>Patients and methods: </strong>This retrospective single-center study included 82 patients (mean age 75.7 years) treated with anterior odontoid screw fixation between 2011 and 2019. Radiographic union was assessed using postoperative imaging. Patient-reported outcome measures (PROMs), including Visual Analog Scale (VAS), Neck Disability Index (NDI), EQ-5D-5L, and SF-36, were obtained at long-term follow-up. Outcomes were compared between patients with and without radiographic union.</p><p><strong>Results: </strong>Radiographic nonunion was observed in 44% of patients. A total of 27 patients completed follow-up assessments. Overall outcomes were favorable, with low pain levels (mean VAS score of 2), minimal disability (NDI mean 7), and good quality of life (EQ-5D-5L mean 0.79). Patients with nonunion demonstrated consistently worse PROMs; however, differences did not reach statistical significance. A significant difference was observed in the EQ-5D-5L anxiety/depression domain (<i>p</i>=0.018), indicating increased psychological burden in the nonunion group.</p><p><strong>Conclusion: </strong>Anterior odontoid screw fixation provides satisfactory long-term clinical outcomes in elderly patients with type II odontoid fractures. Despite a high rate of radiographic nonunion, functional outcomes and quality of life were not significantly impaired. These findings suggest that mechanical stability may be more clinically relevant than complete osseous union. Larger prospective studies are required to confirm these results.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 5","pages":"2894-2907"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of EMP2 and Del-1 in Tamoxifen-resistant Breast Cancer Cells.","authors":"In Hee Lee, Jieun Kang, Jeeyeon Lee, Byeongju Kang, Joon Suk Moon, Ho Yong Park, Eun Ae Kim, Seol-Hwa Jeong, Yee Soo Chae, Soo Jung Lee","doi":"10.21873/invivo.14429","DOIUrl":"10.21873/invivo.14429","url":null,"abstract":"<p><strong>Background/aim: </strong>Endocrine resistance remains a major clinical challenge in hormone receptor-positive (HR+) breast cancer. Although developmental endothelial locus-1 (Del-1) has been implicated in endocrine resistance, the regulatory pathways interacting with Del-1 remain poorly defined. This study aimed to identify molecular components associated with Del-1-driven resistance by performing RNA sequencing in tamoxifen-resistant (TAMR) breast cancer cells following Del-1 knockdown.</p><p><strong>Materials and methods: </strong>RNA sequencing was conducted in TAMR MCF-7 cells following Del-1 silencing to identify Del-1-regulated pathways in endocrine-resistant disease. Among the genes up-regulated after Del-1 suppression, epithelial membrane protein 2 (EMP2) was selected for further investigation due to its reported roles in cellular adhesion, metabolic signaling, and cancer stemness. Gene expression changes were validated using reverse transcription polymerase chain reaction (RT-PCR). Functional studies were performed using small interfering RNA (siRNA)-mediated knockdown of EMP2 or Del-1, followed by proliferation and clonogenic assays.</p><p><strong>Results: </strong>Both EMP2 and Del-1 were up-regulated in luminal breast cancer cell lines. Suppression of Del-1 increased EMP2 expression in TAMR cells, consistent with RNA-seq findings. Notably, EMP2 suppression resulted in an increase in Del-1 expression, suggesting a potential regulatory feedback loop. Furthermore, knockdown of either Del-1 or EMP2 substantially enhanced colony formation in TAMR cells compared with controls.</p><p><strong>Conclusion: </strong>EMP2 may be involved in the regulation of Del-1 expression in TAMR breast cancer cells. Modulation of Del-1 or EMP2 influences cancer stemness in TAMR cells, underscoring the Del-1-EMP2 axis as a potential therapeutic target to overcome endocrine resistance.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 5","pages":"2781-2788"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Efficacy of Co-administered WJ-MSCs and Exosomes in a Rat Pulmonary Fibrosis Model.","authors":"Seung Ho Choi, Hwa Jin Baek, Hyeong Soo Kim, Ji Weon Choi, Sungdeok Min, Wonseok Son","doi":"10.21873/invivo.14424","DOIUrl":"10.21873/invivo.14424","url":null,"abstract":"<p><strong>Background/aim: </strong>Pulmonary fibrosis lacks therapies capable of reversing established fibrosis. Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) show anti-fibrotic promise but are limited by poor engraftment in the fibrotic microenvironment. Evidence from tissue repair models suggests co-delivery of MSC-derived exosomes improves MSC engraftment. Whether WJ-MSCs and their own exosomes produce complementary anti-fibrotic effects in pulmonary fibrosis remains unknown. This study preliminarily evaluated this hypothesis <i>in vivo</i>.</p><p><strong>Materials and methods: </strong>Pulmonary fibrosis was induced in left lungs of male rats using bleomycin. At 21 days after bleomycin injection, animals were assigned to WJ-MSC monotherapy, exosome monotherapy, or combination therapy. At 49 days, these treatment groups, alongside normal and bleomycin-treated controls, were evaluated <i>via</i> gross morphological assessment, lung weight measurement, and histological analysis using Masson's trichrome staining to quantify the fibrotic area.</p><p><strong>Results: </strong>Histological evaluation demonstrated significant fibrotic area expansion in the bleomycin group. While WJ-MSC or exosome monotherapies yielded minimal reduction in fibrotic burden, the combination therapy attenuated the fibrotic area by approximately 50% relative to the bleomycin-treated control, accompanied by a notable restoration of alveolar architecture.</p><p><strong>Conclusion: </strong>Co-administration of WJ-MSCs and their derived exosomes produced substantially greater anti-fibrotic effects than either treatment alone. These preliminary findings suggest exosomes prime the fibrotic microenvironment to enhance WJ-MSC engraftment, with additive paracrine contributions driving superior efficacy. As a single fixed dose at the upper range of previously validated doses was used due to limited animal numbers, future studies with dose-response designs, molecular marker analysis, and functional assessments are warranted.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 5","pages":"2717-2725"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}