Tissue & cell最新文献

{"title":"The clinical significance and biological function of tropomyosin 3 in ulcerative colitis.","authors":"Xue-Qin Zhang, Jian-Mei Li, Feng-Qian Wang, Yan-Hui Ren, Shi-Xian Wu, Yao Wu, Yuan Tang","doi":"10.1016/j.tice.2025.102770","DOIUrl":"10.1016/j.tice.2025.102770","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is a lifelong chronic inflammatory disease that is characterized by the absence of specific markers for diagnosis and prognosis. TPM3 is an integral component of the thin filament, responsible for the structural stability of actin filaments and modulation of cytoskeletal function. This study investigated the regulatory role of TPM3 in UC and its potential mechanisms.</p><p><strong>Methods: </strong>At the clinical level, TPM3 levels were assessed in serum and mucosal tissues of UC and other enteric disease. At the cellular level, the effects of TMP3 overexpressing lentivirus on Caco-2 cell phenotype and the barrier of IL-1β-induced UC model were explored. At the animal level, the effects of TMP3 overexpressing lentivirus on symptoms and colonic damage in a DSS-induced UC model were explored.</p><p><strong>Results: </strong>TPM3 expression in serum of UC patients was significantly lower than that of other enteric disease, and TPM3 levels in the intestinal mucosa showed a negative correlation with the Mayo score of UC patients. TPM3 overexpression alleviates IL-1β-induced apoptosis and inhibition of invasion and migration in UC model in vitro. In monolayer Caco-2 cells, TPM3 overexpression rescued the IL-1β-induced decrease in transepithelial electrical resistance and tight junction markers (ZO-1 and Occludin) and increase in permeability. In animal experiments, TPM3 overexpression increased body weight and colon length and decreased disease activity index in a DSS-induced UC model. In tissue staining, it alleviated pathological damage and upregulated Occuludin and TPM3 levels in the colon.</p><p><strong>Conclusion: </strong>TPM3 levels correlated with UC disease course and TPM3 overexpression alleviated symptoms/phenotypes and barrier damage in UC models in vivo and in vitro. TPM3 may serve as a potential novel biomarker for UC diagnosis and prognosis.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"102770"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of angiotensin type 2 receptor-mediated nitric oxide pathway in angiotensin II-induced vasorelaxation: Roles of potassium channels.","authors":"Chinar M Mohammed, Omar A M Al-Habib","doi":"10.1016/j.tice.2025.102761","DOIUrl":"10.1016/j.tice.2025.102761","url":null,"abstract":"<p><p>A variety of biological functions is attributed to the renin-angiotensin system (RAS). One of them is regulating vascular tone through its final effector Angiotensin II (Ang II). Ang II action is mediated by the Angiotensin type 1 receptor (AT1-R) which plays a role in vasoconstriction, and Angiotensin type 2 receptor (AT2-R) which may result in vascular relaxation through the releasing of endothelium mediates relaxation factors such as Nitric Oxide (NO). Therefore, this study investigated the role of AT2-R in vasodilation after blocking the effect of AT1-R in the rat aorta. Furthermore, it is to determine whether or not Ang II through NO has a role in rat aorta dilation via using valsartan. For control isolated aortic rings were preincubated with Valsartan (AT1- R inhibitor) and then stimulated with angiotensin II dose-dependent. For treating aortic rings different blockers and inhibitors were used. Pd123177 (AT2- R inhibitor) (20 µM), an inhibitor of PKA H-89 (10 µM), eNOS inhibitor L-NAME (0.3 mM), with group of K channel blockers such as TEA (1 mM), 4-AP (1 mM), BaCl2 (1 mM), clotrimazole (0.03 mM) and GLIB (0.01 mM). Our analysis demonstrates vasodilation in aortic rings induced by Ang II after blocking ATI-R and this response was highly reliant on PKA/eNOS and cyclic guanosine monophosphate (cGMP). The data from this investigation provided evidence that Ca2 + activated K+ channels (KCa) and Voltage-dependent K channel (KV) mediated Ang II vasorelaxation. Finally, these results indicate that angiotensin II primarily induces dilatation AT2-R after inhibiting the angiotensin AT1 receptor through a cascade of signaling pathways involving many enzymes and plasma membrane protein channels.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"102761"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taxifolin mitigates cisplatin-induced testicular damage by reducing inflammation, oxidative stress, and apoptosis in mice.","authors":"Alayn' Al-Marddyah A Al-Khawalde, Mohammad H Abukhalil, Osama Y Althunibat, Fatima A Jaber, Fatima S Alaryani, Alaa M Saleh, Aishah E Albalawi, Reem H Alhasani","doi":"10.1016/j.tice.2025.102767","DOIUrl":"10.1016/j.tice.2025.102767","url":null,"abstract":"<p><p>Cisplatin (CIS) is effective against various cancers but causes significant side effects, including testicular damage. This study investigated the effects of taxifolin (TX), a potent flavonoid with well-known benefits, against CIS-induced testicular injury. Mice received TX (25 and 50 mg/kg) orally for 14 days, with a single injection of CIS (7 mg/kg) on day 8. CIS significantly impaired sperm parameters (motility, viability, and count) and caused notable histopathological alterations in testicular tissue. CIS-treated testicular tissue exhibited elevated MDA and protein carbonyl levels, alongside decreased antioxidant defenses, including GSH, SOD, and catalase activities. TX significantly mitigated the deterioration of sperm parameters and prevented testicular tissue damage. It also restored antioxidant levels and reduced MDA and protein carbonyl contents. Furthermore, CIS elevated pro-inflammatory markers (NF-κB p65, TNF-α, and IL-1β) and apoptosis markers (Bax and caspase-3), while reducing anti-apoptotic Bcl-2 levels. TX effectively suppressed NF-κB activation, reduced pro-inflammatory cytokine production, and inhibited apoptosis in CIS-treated mice. Overall, TX alleviated CIS-induced oxidative stress, inflammation, apoptosis, and testicular damage, thereby improving sperm quality. These findings emphasize TX's potential as a protective agent against CIS-induced testicular damage and warrant further research in human applications.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"102767"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CLMP increases 5-fluorouracil sensitivity in colorectal cancer through the inhibition of autophagy.","authors":"Kun Yu, Hongjiang Pu, Xuan Zhang, Quan Yang, Weimin Wang, Wenliang Li, Ziyu Li","doi":"10.1016/j.tice.2025.102771","DOIUrl":"10.1016/j.tice.2025.102771","url":null,"abstract":"<p><strong>Background: </strong>We aimed to explore the biological function of CLMP in colorectal cancer (CRC) and to determine the effect of CLMP on 5-fluorouracil (5-FU) sensitivity in CRC.</p><p><strong>Methods: </strong>Sixteen pairs of CRC tissues and paracancerous tissues were collected. Immortalized intestinal epithelial cell lines and human CRC cell lines were purchased, and the cells were treated with DMSO and 5-FU. RTqPCR, western blotting, CCK8, colony formation, scratch, and Transwell assays were performed to determine the molecular mechanism of CLMP in the regulation of autophagy and sensitivity to 5-FU in CRC cells.</p><p><strong>Results: </strong>CLMP was expressed at low levels in CRC tissues. The upregulation of CLMP expression could inhibit cell proliferation, colony number, migration and invasion and increase the sensitivity of CRC cells to 5-FU. Mechanistic studies revealed that the overexpression of CLMP could block the activation of the PI3K/AKT signaling pathway, inhibit autophagy, and increase the chemosensitivity of CRC cells to 5-FU.</p><p><strong>Conclusion: </strong>CLMP overexpression can reduce the level of autophagy and increase the sensitivity of CRC to 5-FU, providing a potential target for the treatment of CRC.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"102771"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural changes in the ganglionic layer of the rat cerebellar cortex due to the use of monosodium glutamate and sodium nitrite in combination.","authors":"Bohdan Kononov, Serhii Bilash, Ihor Tretiak, Maryna Kononova, Olena Pronina, Mykhailo Koptev, Angelina Pirog-Zakaznikova, Svitlana Donchenko, Yaryna Oliinichenko, Vladyslav Oleksiienko","doi":"10.1016/j.tice.2025.102760","DOIUrl":"10.1016/j.tice.2025.102760","url":null,"abstract":"<p><strong>Background: </strong>The issue of using many food additives in food is becoming increasingly relevant. The effect of these substances on the nervous system, namely the cerebellum, is not unrelated. There are studies on the impact of food additives individually, but their combined effect has not been studied sufficiently. Therefore, the aim of our study was to determine structural changes in rats' ganglionic layer of the cerebellar cortex under the influence of monosodium glutamate and sodium nitrite in combination.</p><p><strong>Methods: </strong>The experiment involved 84 white Wistar laboratory rats, which were divided into a control group and five experimental groups. The obtained cerebellar samples were paraffin-embedded and histological sections (3-4) μm thick were made. These sections were stained with hematoxylin, eosin, and silver impregnated by Grimmelius.</p><p><strong>Results: </strong>After calculating the average thickness of the cerebellar cortex ganglionic layer at different administration periods of monosodium glutamate and sodium nitrite in combination, significant changes were observed after week 1, where this indicator was 1.18 times less than in the control. Also, a decrease in the average thickness was observed after the 4th and 12th and a significant decrease in the 16th week of the study, namely by 1.61 times, 1.43 times and 1.77 times, respectively. It indicates substantial structural changes in the ganglionic layer.</p><p><strong>Conclusions: </strong>The study found that the ganglionic layer is formed of a single row of Purkinje cells, and they, in turn, are the main functional link in the entire grey matter of the cerebellum, which suggests that the use of a complex of food additives causes functional disorders of the cerebellum as a whole.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"102760"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the role of HIF-1α in allergic rhinitis: A key regulator of epithelial barrier integrity via PI3K pathway","authors":"Zhuo Wu ,&nbsp;Yongbo Zhang ,&nbsp;Changzeng Zhou ,&nbsp;Guxuan Zhang ,&nbsp;Lei He ,&nbsp;Ming Tang","doi":"10.1016/j.tice.2025.102898","DOIUrl":"10.1016/j.tice.2025.102898","url":null,"abstract":"<div><h3>Background</h3><div>Allergic rhinitis (AR) ranks among the most prevalent nasal disorders worldwide. Epithelial cells are the initial physiological barrier against allergen entry, and play a vital protective role. The precise role of hypoxia-inducible factor 1-alpha (HIF-1α) inhibitors in nasal epithelial cell injury in AR is still unknown, despite their confirmed association with nasal inflammation in AR models.</div></div><div><h3>Methods</h3><div>An interleukin-13 (IL-13)-induced AR cell model has been employed to investigate how HIF-1α inhibition impacts nasal epithelial cells (JME/CF15). Cell viability, inflammatory cytokines, mucosal remodeling factors, and the tight junction protein zonula occludens-1 (ZO-1) were evaluated using cell counting kit-8, enzyme-linked immunosorbent assay, Western blot, and immunofluorescence. The influences of phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways have been examined.</div></div><div><h3>Results</h3><div>PX-478 (a HIF-1α inhibitor) alleviated IL-13-induced epithelial barrier dysfunction by upregulating ZO-1 and reducing levels of inflammatory and remodeling factors. Mechanistically, HIF-1α activated the PI3K/MEK signaling pathway, exacerbating epithelial barrier disruption and inflammatory responses. Knockdown of HIF-1α suppressed PI3K pathway activation, mitigating inflammation and restoring barrier integrity. However, these protective effects were reversed by a PI3K agonist.</div></div><div><h3>Conclusions</h3><div>HIF-1α aggravates AR by promoting inflammation, mucosal remodeling, and epithelial barrier dysfunction via PI3K pathway activation. This finding not only enriches our understanding of AR pathophysiology but also highlights HIF-1α and its downstream signaling pathways as prospective therapeutic targets for AR.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"Article 102898"},"PeriodicalIF":2.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3-mediated m6A modification of MT1G inhibits papillary thyroid carcinoma cell growth and metastasis via Wnt/β-catenin pathway","authors":"Jie Liu,&nbsp;Lei Yao,&nbsp;Yating Chen,&nbsp;Xueyu Wang,&nbsp;Kun Wang","doi":"10.1016/j.tice.2025.102902","DOIUrl":"10.1016/j.tice.2025.102902","url":null,"abstract":"<div><h3>Background</h3><div>Downregulation of metallothionein 1<!--> <!-->G (MT1G) has been demonstrated in papillary thyroid carcinoma (PTC) tissues. However, the underlying molecular mechanisms of MT1G in PTC progression need to be further explored.</div></div><div><h3>Methods</h3><div>MT1G and methyltransferase-like 3 (METTL3) mRNA levels were tested by quantitative real-time PCR. The protein levels of MT1G, METTL3, Wnt3A and β-catenin were measured by western blot. Cell proliferation, apoptosis, invasion and migration were measured by cell counting kit 8 assay, colony formation assay, EdU assay, flow cytometry, transwell assay and wound healing assay. MeRIP analysis was used to detect the MT1G methylation. The interaction between METTL3 and MT1G was evaluated using RIP assay and dual-luciferase reporter assay. A mouse xenograft model was also constructed to explore the roles of METTL3 and MT1G <em>in vivo</em>.</div></div><div><h3>Results</h3><div>MT1G expression was downregulated in PTC, and its overexpression suppressed PTC cell growth, invasion and migration. METTL3-regulated m6A modification enhanced MT1G mRNA stability. Overexpression of METTL3 repressed PTC cell growth and metastasis, and this effect was reversed by MT1G knockdown. Besides, METTL3/MT1G axis could inhibit the activity of Wnt/β-catenin pathway. Meanwhile, METTL3 enhanced MT1G expression to suppress PTC tumor growth through Wnt/β-catenin pathway <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>METTL3-mediated m6A modification of MT1G inhibited PTC cell growth and metastasis via inactivating the Wnt/β-catenin pathway.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"Article 102902"},"PeriodicalIF":2.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracellular alterations, vacuolization and bypass mechanism by SARS-CoV-2 infection could be the possible basis of respiratory distress and hypoxia","authors":"Shareef Mohammed Buvvaji ,&nbsp;Vinod Joshi ,&nbsp;Annette Angel ,&nbsp;Bennet Angel ,&nbsp;Poorna Khaneja ,&nbsp;Ramesh Joshi","doi":"10.1016/j.tice.2025.102896","DOIUrl":"10.1016/j.tice.2025.102896","url":null,"abstract":"<div><div>Severe Acute Respiratory Syndrome Coronavirus-2 causes mild to severe Acute Respiratory Distress Syndrome, Pneumonia and lung tissue damage. This leads to sub performance in the pulmonary gaseous exchange by the alveolar cells causing hypoxia associated with clinical severities/mortality. The exact cellular basis of the pulmonary malfunction resulting into death of approximately 7.1 million people needs to be fully studied. Understanding the intracellular alterations in pulmonary cells caused by viral infection could prove to be a significant step in our attempts to revert the respiratory efficiency of the patients through appropriate therapeutic interventions. We have undertaken In-Vitro studies to understand the pathogenesis of SARS-CoV-2 in alveoli. We cultured the Alveolar Epithelium (A549 and L-132), Fibroblasts (WI-38), Human Pulmonary Artery Endothelial Cells (HPAEC-c), and African Green Monkey Kidney Epithelial Cells (Vero-E6) and infected them with SARS-CoV-2. Vacuoles in infected Alveolar Type-2 cells, cytoskeletal deformation, fragmentation of mitochondria in alveolar and arterial endothelial cells, loss of glycoclayx in endothelial cells and a unique bypass exit mechanism of virus were observed as major intracellular changes due to infection. The bypass exit of the daughter virions from lung cells along with loss of glycoclayx due to virus overburdening is reported as mechanism of propagation of infection towards multiple organs. We report that formation of numerous vacuoles in infected Alveolar Type-2 cells and the SARS-CoV-2 virions occupying these vacuoles could hamper the trans cytoplasmic trafficking of surfactant mixed inspired air and its subsequent transfer into venous blood through cell membranes of Alveolar Type −2 Cells and Capillary Wall Cells of pulmonary vein. The possible use of repurposed Nitroglycerine based drug to retrieve required intracellular cytoplasmic viscosity of the Alveolar type 2 cells has also been suggested.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"Article 102896"},"PeriodicalIF":2.7,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iguratimod modulates osteoclast differentiation in rheumatoid arthritis: Insights into AMPK/HIF-1α signaling pathway regulation","authors":"Huang Ying ,&nbsp;Li Xingyi ,&nbsp;Liu Jun ,&nbsp;Li Peiting ,&nbsp;Yue Xin ,&nbsp;Zeng Jiashun ,&nbsp;Li Long","doi":"10.1016/j.tice.2025.102894","DOIUrl":"10.1016/j.tice.2025.102894","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) leads to joint deformities and diminishes quality of life if not managed promptly. Investigating Iguratimod effects on osteoclast differentiation in RA patients could provide insights into disease management.</div></div><div><h3>Methods</h3><div>Peripheral blood mononuclear cells (PBMCs) were extracted from blood samples taken from RA patients. TRAP staining confirmed the ability of these cells to differentiate into osteoclasts. Those cells were treated with Iguratimod, AMPK agonist (AICAR), and HIF-1α interference (PX-478) during osteoclast induction. CCK8, flow cytometry, ELISA, qPCR, and WB were used to detect changes after exposure in each group.</div></div><div><h3>Results</h3><div>Iguratimod, AICAR and PX-478 reduced osteoclast formation and viability while promoting apoptosis. ELISA results showed that exposure with Iguratimod, AICAR and PX-478 significantly reduced the levels of CXCL8, CCL20, TNF-α, IL-1, IL-6, IL-17 and TPRA secreted by PBMCs from RA patients. In addition, the results demonstrate that Iguratimod, along with AICAR, PX-478, and Leflunomide, significantly suppresses the expression of osteoclast-specific markers (HIF-1α, TRAP, CTSK, CTR, MMP9, and RANK) at both mRNA and protein levels. Notably, Iguratimod, AICAR, and Leflunomide increase the expression of AMPK and p-AMPK, while PX-478 decreases their expression.</div></div><div><h3>Conclusions</h3><div>Iguratimod potentially modulates AMPK/HIF-1α pathway, thereby suppressing release of inflammatory factors and influencing differentiation of peripheral blood osteoclasts in RA patients. These findings suggest promising therapeutic strategies for exposure of joint deformities associated with RA.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"Article 102894"},"PeriodicalIF":2.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143800263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wound-healing effects of frozen-thawed allogeneic fibroblast sheet transplantation and xenogeneic fibroblast cell sheet transplantation cultured on a new substrate","authors":"Yutaro Suto ,&nbsp;Koji Ueno ,&nbsp;Hiroshi Kurazumi ,&nbsp;Wataru Kawai ,&nbsp;Keita Yoshida ,&nbsp;Koji Harada ,&nbsp;Tomoko Kondo ,&nbsp;Tomoaki Murata ,&nbsp;Taro Takami ,&nbsp;Kimikazu Hamano","doi":"10.1016/j.tice.2025.102888","DOIUrl":"10.1016/j.tice.2025.102888","url":null,"abstract":"<div><div>This study aimed to investigate the therapeutic effect of cryopreserved fibroblast cell sheets cultured using new substrates on cutaneous ulcers in a mouse allogenic and xenogeneic model. Since cell sheets are very fragile, transplanting cell sheets requires some ingenuity. This study demonstrates the simplicity of using a new substrate, development code CY-1, a hydrophilic-treated thermoplastic resin film, to perform a series of processes from cell culture and cryopreservation thawing to cell sheet transplantation. In this study, fibroblasts were cultured on CY-1, then frozen with a cell preservation solution using a 3D freezer. Freeze-thawed fibroblasts were transplanted to the target position, and CY-1 was removed at the time of transplant. The freeze-thawed allogenic fibroblast sheets cultured on CY-1 exhibited significantly higher therapeutic effects on cutaneous defects in diabetic C57BL/6 mice compared to those without sheet transplantation (control group), consistent with hair follicle regeneration on day 15. We performed immunostaining on the day 15, and found that the allogenic fibroblast sheets group had significantly fewer CD3-positive cells than in the control group (allogenic vs. control: 302 ± 68.7 vs. 389 ± 30.9 [p = 0.03]). Cell viability and VEGF concentration were similar between freeze-thawed human fibroblasts cultured on CY-1 at 24 hr after thawing compared to nonfrozen human fibroblasts. HGF concentrations significantly increased in freeze-thawed human fibroblasts cultured on CY-1 at 24 hr after thawing compared to nonfrozen human fibroblasts (nonfrozen vs. freeze-thawed: 839 ± 50.6 vs. 1750 ± 118 [p &lt; 0.01]). Freeze-thawed human fibroblast sheets cultured on CY-1 exhibited significantly higher therapeutic effects for cutaneous defects of immunodeficient mice compared to control group. There are significantly more active HGF in the surrounding murine tissue of the xenogeneic fibroblast sheet on the day 2 than those in control group (xenogeneic vs. control: 600 ± 116 vs. 437 ± 71 [p &lt; 0.05]). Therefore, freeze-thawed fibroblast sheets cultured on CY-1 can be effective for refractory cutaneous ulcers in clinical practice.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"Article 102888"},"PeriodicalIF":2.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}