Tissue engineering and regenerative medicine最新文献

{"title":"Macrophage Polarization: A Novel Target and Strategy for Pathological Scarring.","authors":"Xinyi Wang, Dewu Liu","doi":"10.1007/s13770-024-00669-7","DOIUrl":"10.1007/s13770-024-00669-7","url":null,"abstract":"<p><strong>Background: </strong>Abnormal scarring imposes considerable challenges and burdens on the lives of patients and healthcare system. Macrophages at the wound site are found to be of great concern to overall wound healing. There have been many studies indicating an inextricably link between dysfunctional macrophages and fibrotic scars. Macrophages are not only related to pathogen destruction and phagocytosis of apoptotic cells, but also involved in angiogenesis, keratinization and collagen deposition. These abundant cell functions are attributed to specific heterogeneity and plasticity of macrophages, which also add an extra layer of complexity to correlational researches.</p><p><strong>Methods: </strong>This article summarizes current understanding of macrophage polarization in scar formation and several prevention and treatment strategies on pathological scarring related to regulation of macrophage behaviors by utilizing databases such as PubMed, Google Scholar and so on.</p><p><strong>Results: </strong>There are many studies proving that macrophages participate in the course of wound healing by converting their predominant phenotype. The potential of macrophages in managing hypertrophic scars and keloid lesions have been underscored.</p><p><strong>Conclusion: </strong>Macrophage polarization offers new prevention strategies for pathological scarring. Learning about and targeting at macrophages may be helpful in achieving optimum wound healing.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1109-1124"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354415","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":"Preparation and Evaluation of Poloxamer/Carbopol In-Situ Gel Loaded with Quercetin: In-Vitro Drug Release and Cell Viability Study.","authors":"Pinxuan Zheng, Xueying Liu, Yanqing Jiao, Xuran Mao, Zhaorong Zong, Qi Jia, Heng Bo Jiang, Eui-Seok Lee, Qi Chen","doi":"10.1007/s13770-024-00671-z","DOIUrl":"10.1007/s13770-024-00671-z","url":null,"abstract":"<p><strong>Background: </strong>Periodontitis is a severe chronic inflammatory disease, whose traditional systemic antimicrobial therapy faces great limitations. In-situ gels provide an effective solution as an emerging local drug delivery system.</p><p><strong>Methods: </strong>In this study, the novel thermosensitive poloxamer/carbopol in-situ gels loaded with 20 μmol/L quercetin for the treatment of periodontitis were prepared by cold method. Thirteen batches of in-situ gels based on two independent factors (X₁: poloxamer 407 and X₂: carbopol 934P) were designed and optimized by the statistical method of central composite design (CCD). The transparency, pH, injectability, viscosity, gelation temperature, gelation time, elasticity modulus, degradation rate and in-vitro drug release studies of the batches were evaluated, and the percentage of drug release in the first hour, the time required for 90% drug release, gelation temperature, and gelation time were selected as dependent variables.</p><p><strong>Results: </strong>These two independent factors significantly affected the four dependent variables (p < 0.05). The optimization result displayed that the optimized concentration of poloxamer 407 was 20.84% (w/v), and carbopol 934P was 0.5% (w/v). The optimized formulation showed a clear appearance (++), acceptable injectability (Pass), viscosity(151,798 mPa s), gelation temperature (36 °C), gelation time (213 s), preferable cell viability and cell proliferation, conformed to first-order release kinetics, and had a significant antibacterial effect.</p><p><strong>Conclusions: </strong>The article demonstrates the great potential of the quercetin in-situ gel as an effective treatment for periodontitis.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1153-1171"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565231","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":"Perfusion Bioreactor Conditioning of Small-diameter Plant-based Vascular Grafts.","authors":"Nicole Gorbenko, John C Vaccaro, Ryan Fagan, Robert A Cerro, Jonah M Khorrami, Lucia Galindo, Nick Merna","doi":"10.1007/s13770-024-00670-0","DOIUrl":"10.1007/s13770-024-00670-0","url":null,"abstract":"<p><strong>Background: </strong>Vascular grafts are mainly composed of synthetic materials, but are prone to thrombosis and intimal hyperplasia at small diameters. Decellularized plant scaffolds have emerged that provide promising alternatives for tissue engineering. We previously developed robust, endothelialized small-diameter vessels from decellularized leatherleaf viburnum. This is the first study to precondition and analyze plant-based vessels under physiological fluid flow and pressure waveforms. Using decellularized leatherleaf viburnum as tissue-engineered grafts for implantation can have profound impacts on healthcare due to their biocompatibility and cost-effective production.</p><p><strong>Methods: </strong>A novel perfusion bioreactor was designed, capable of accurately controlling fluid flow rate and pressure waveforms for preconditioning of small-diameter vascular grafts. A closed-loop system controlled pressure waveforms, mimicking physiological values of 50-120 mmHg at a frequency of 8.75 Hz for fluid flow reaching 5 mL/min. Plant-based vascular grafts were recellularized with endothelial and vascular smooth muscle cells and cultured for up to 3 weeks in this bioreactor. Cell density, scaffold structure and mechanics, thrombogenicity, and immunogenicity of grafts were evaluated.</p><p><strong>Results: </strong>Bioreactor treatment with fluid flow significantly increased luminal endothelial cell density, while pressure waveforms reduced thrombus formation and maintained viable vascular smooth muscle cells within inner layers of grafts compared to static controls. Suture retention of grafts met transplantation standards and white cell viability was suitable for vascular remodeling.</p><p><strong>Conclusion: </strong>Low thrombogenicity of endothelialized leatherleaf viburnum holds great potential for vascular repair. This study provides insight into benefits of conditioning plant-based materials with hemodynamic forces at higher frequencies that have not previously been investigated.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1189-1201"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362136","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":"Evaluation of Bi-layer Silk Fibroin Grafts for Inlay Vaginoplasty in a Rat Model.","authors":"Travis Nguyen, Gokhan Gundogdu, Christina Bottini, Ambika K Chaudhuri, Joshua R Mauney","doi":"10.1007/s13770-024-00653-1","DOIUrl":"10.1007/s13770-024-00653-1","url":null,"abstract":"<p><strong>Background: </strong>Autologous tissues derived from bowel, buccal mucosa and skin are primarily used to repair or replace diseased vaginal segments as well as create neovaginas for male-to-female transgenders. These grafts are often limited by scarce tissue supply, donor site morbidity and post-operative complications. Bi-layer silk fibroin (BLSF) biomaterials represent potential alternatives for vaginoplasty given their structural strength and elasticity, low immunogenicity, and processing flexibility. The goals of the current study were to assess the potential of acellular BLSF scaffolds for vaginal tissue regeneration in respect to conventional small intestinal submucosal (SIS) matrices in a rat model of vaginoplasty.</p><p><strong>Methods: </strong>Inlay vaginoplasty was performed with BLSF and SIS scaffolds (N = 21 per graft) in adult female rats for up to 2 months of implantation. Nonsurgical controls (N = 4) were investigated in parallel. Outcome analyses included histologic, immunohistochemical and histomorphometric evaluations of wound healing patterns; µ-computed tomography (CT) of vaginal continuity; and breeding assessments.</p><p><strong>Results: </strong>Animals in both scaffold cohorts exhibited 100% survival rates with no severe post-operative complications. At 2 months post-op, µ-CT analysis revealed normal vaginal anatomy and continuity in both graft groups similar to controls. In parallel, BLSF and SIS grafts also induced comparable constructive remodeling patterns and were histologically equivalent in their ability to support formation of vascularized vaginal neotissues with native tissue architecture, however with significantly less smooth muscle content. Vaginal tissues reconstructed with both implants were capable of supporting copulation, pregnancy and similar amounts of live births.</p><p><strong>Conclusions: </strong>BLSF biomaterials represent potential \"off-the-shelf\" candidates for vaginoplasty.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"985-994"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184646","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":"Glycinamide Facilitates Nanocomplex Formation and Functions Synergistically with Bone Morphogenetic Protein 2 to Promote Osteoblast Differentiation In Vitro and Bone Regeneration in a Mouse Calvarial Defect Model.","authors":"Sang-Hyeon Nam, Ju Ang Kim, Soomin Lim, Su Jeong Lee, Chun-Ho Kim, Jong-Sup Bae, Yong Chool Boo, Young-Jin Kim, Eui Kyun Park","doi":"10.1007/s13770-024-00657-x","DOIUrl":"10.1007/s13770-024-00657-x","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to identify glycine analogs conducive to the formation of cell-absorbable nanocomplexes, enhancing collagen synthesis and subsequent osteogenesis in combination with BMP2 for improved bone regeneration.</p><p><strong>Methods: </strong>Glycine and its derivatives were assessed for their effects on osteogenic differentiation in MC3T3-E1 cells and human bone marrow mesenchymal stem cells (BMSCs) under osteogenic conditions or with BMP2. Osteogenic differentiation was assessed through alkaline phosphatase staining and real-time quantitative polymerase chain reaction (RT-qPCR). Nanocomplex formation was examined via scanning electron microscopy, circular dichroism, and ultraviolet-visible spectroscopy. In vivo osteogenic effects were validated using a mouse calvarial defect model, and bone regeneration was evaluated through micro-computed tomography and histomorphometric analysis.</p><p><strong>Results: </strong>Glycine, glycine methyl ester, and glycinamide significantly enhanced collagen synthesis and ALP activity in conjunction with an osteogenic medium (OSM). GA emerged as the most effective inducer of osteoblast differentiation marker genes. Combining GA with BMP2 synergistically stimulated ALP activity and the expression of osteoblast markers in both cell lines. GA readily formed nanocomplexes, facilitating cellular uptake through strong electrostatic interactions. In an in vivo calvarial defect mouse model, the GA and BMP2 combination demonstrated enhanced bone volume, bone volume/tissue volume ratio, trabecular numbers, and mature bone formation compared to other combinations.</p><p><strong>Conclusion: </strong>GA and BMP2 synergistically promoted in vitro osteoblast differentiation and in vivo bone regeneration through nanocomplex formation. This combination holds therapeutic promise for individuals with bone defects, showcasing its potential for clinical intervention.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1093-1107"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493522","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":"Zinc-Alpha-2-Glycoprotein Peptide Downregulates Type I and III Collagen Expression via Suppression of TGF-β and p-Smad 2/3 Pathway in Keloid Fibroblasts and Rat Incisional Model.","authors":"Shin Hyun Kim, Jung Min Oh, Hyun Roh, Kee-Won Lee, Ju Hee Lee, Won Jai Lee","doi":"10.1007/s13770-024-00664-y","DOIUrl":"10.1007/s13770-024-00664-y","url":null,"abstract":"<p><strong>Background: </strong>Keloids and hypertrophic scars result from abnormal collagen accumulation and the inhibition of its degradation. Although the pathogenesis remains unclear, excessive accumulation of the extracellular matrix (ECM) is believed to be associated with the TGF-β/SMAD pathway. Zinc-alpha-2-glycoprotein (ZAG) inhibits TGF-β-mediated epithelial-to-mesenchymal transdifferentiation and impacts skin barrier functions. In this study, we investigated the potential of a small ZAG-derived peptide against hypertrophic scars and keloids.</p><p><strong>Methods: </strong>The study examined cell proliferation and mRNA expression of collagen types I and III in human dermal fibroblast (HDF) cell lines and keloid-derived fibroblasts (KF) following ZAG peptide treatment. A rat incisional wound model was used to evaluate the effect of ZAG peptide in scar tissue.</p><p><strong>Results: </strong>Significantly lower mRNA levels of collagen types I and III were observed in ZAG-treated fibroblasts, whereas matrix metalloproteinase (MMP)-1 and MMP-3 mRNA levels were significantly increased in HDFs and KFs. Furthermore, ZAG peptide significantly reduced protein expression of collagen type I and III, TGF-β1, and p-Smad2/3 complex in KFs. Rat incisional scar models treated with ZAG peptide presented narrower scar areas and reduced immature collagen deposition, along with decreased expression of collagen type I, α-SMA, and p-Smad2/3.</p><p><strong>Conclusion: </strong>ZAG peptide effectively suppresses the TGF-β and p-Smad2/3 pathway and inhibits excessive cell proliferation during scar formation, suggesting its potential therapeutic implications against keloids and hypertrophic scars.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1079-1092"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894375","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":"Multifunctional Microneedle Patch with Diphlorethohydroxycarmalol for Potential Wound Dressing.","authors":"Tae-Hee Kim, Min-Sung Kim, Nam-Gyun Kim, Nguyen Vu Linh, Hien Van Doan, Young-Mog Kim, Sang-Hyug Park, Won-Kyo Jung","doi":"10.1007/s13770-024-00655-z","DOIUrl":"10.1007/s13770-024-00655-z","url":null,"abstract":"<p><strong>Background: </strong>Treatment of skin wounds with diverse pathological characteristics presents significant challenges due to the limited specific and efficacy of current wound healing approaches. Microneedle (MN) patches incorporating bioactive and stimulus materials have emerged as a promising strategy to overcome these limitations and integrating bioactive materials with anti-bacterial and anti-inflammatory properties for advanced wound dressing.</p><p><strong>Methods: </strong>We isolated diphlorethohydroxycarmalol (DPHC) from Ishige okamurae and assessed its anti-inflammatory and anti-bacterial effects on macrophages and its antibacterial activity against Cutibacterium acnes. Subsequently, we fabricated polylactic acid (PLA) MN patches containing DPHC at various concentrations (0-0.3%) (PDPHC MN patches) and evaluated their mechanical properties and biological effects using in vitro and in vivo models.</p><p><strong>Resutls: </strong>Our findings demonstrated that DPHC effectively inhibited nitric oxide production in macrophages and exhibited rapid bactericidal activity against C. acnes. The PDPHC MN patches displayed potent antibacterial effects without cytotoxicity. Moreover, in 2,4-Dinitrochlorobenzene-stimulated mouse model, the PDPHC MN patches significantly suppressed inflammatory response and cutaneous lichenification.</p><p><strong>Conclusion: </strong>The results suggest that the PDPHC MN patches holds promise as a multifunctional wound dressing for skin tissue engineering, offering antibacterial properties and anti-inflammatory properties to promote wound healing process.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1007-1019"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321703","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":"Reduced Cell Migration in Human Chondrocyte Sheets Increases Tissue Stiffness and Cartilage Protein Production.","authors":"Sopita Wongin-Sangphet, Pojchong Chotiyarnwong, Kwanchanok Viravaidya-Pasuwat","doi":"10.1007/s13770-024-00662-0","DOIUrl":"10.1007/s13770-024-00662-0","url":null,"abstract":"<p><strong>Background: </strong>Chondrogenic differentiation medium (CDM) is usually used to maintain chondrogenic activity during chondrocyte sheet production. However, tissue qualities remain to be determined as to what factors improve cell functions. Moreover, the relationship between CDM and cell migration proteins has not been reported.</p><p><strong>Method: </strong>In this study, the effect of CDM on the behavior of chondrocyte sheets was investigated. Structural analysis, mechanical testing and proteomics were performed to observe tissue qualities. The relationship between CDM and cell migration proteins were investigated using time-lapse observations and bioinformatic analysis.</p><p><strong>Results: </strong>During 48 h, CDM affected the chondrocyte behaviors by reducing cell migration. Compared to the basal medium, CDM impacted the contraction of monolayered chondrocyte sheets. At day 7, the contracted sheets increased tissue thickness and improved tissue stiffness. Cartilage specific proteins were also upregulated. Remarkedly, the chondrocyte sheets in CDM displayed downregulated proteins related to cell migration. Bioinformatic analysis revealed that TGFβ1 was shown to be associated with cartilage functions and cell migration. Pathway analysis of chondrocyte sheets in CDM also revealed the presence of a TGFβ pathway without activating actin production, which might be involved in synthesizing cartilage-specific proteins. Cell migration pathway showed MAPK signaling in both cultures of the chondrocyte sheets.</p><p><strong>Conclusion: </strong>Reduced cell migration in the chondrocyte sheet affected the tissue quality. Using CDM, TGFβ1 might trigger cartilage protein production through the TGFβ pathway and be involved in cell migration via the MAPK signaling pathway. Understanding cell behaviors and their protein expression would be beneficial for developing high-quality tissue-engineered cartilage.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1021-1036"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735050","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":"Exosomes Derived from Rejuvenated Stem Cells Inactivate NLRP3 Inflammasome and Pyroptosis of Nucleus Pulposus Cells via the Transfer of Antioxidants.","authors":"Shuai Peng, Xiangyang Liu, Lei Chang, Bin Liu, Mingyan Zhang, Yan Mao, Xiongjie Shen","doi":"10.1007/s13770-024-00663-z","DOIUrl":"10.1007/s13770-024-00663-z","url":null,"abstract":"<p><strong>Background: </strong>Accumulating evidence supports the potential of exosomes as a promising therapeutic approach for intervertebral disc degeneration (IDD). Nevertheless, enhancing the efficiency of exosome treatment remains an urgent concern. This study investigated the impact of quercetin on the characteristics of mesenchymal stem cells (MSCs) and their released exosomes.</p><p><strong>Methods: </strong>Exosomes were obtained from quercetin pre-treated MSCs and quantified for the production based on nanoparticle tracking and western blot analysis. The molecules involved in the secretion and cargo sorting of exosomes were investigated using western blot and immunofluorescence analysis. Based on the in vitro biological analysis and in vivo histological analysis, the effects of exosomes derived from conventional or quercetin-treated MSCs on nucleus pulposus (NP) cells were compared.</p><p><strong>Results: </strong>A significant enhancement in the production and transportation efficiency of exosomes was observed in quercetin-treated MSCs. Moreover, the exosomes derived from quercetin-treated MSCs exhibited a greater abundance of antioxidant proteins, specifically superoxide dismutase 1 (SOD1), which inhibit the activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome in NP cells. Through in vitro and in vivo experiments, it was elucidated that exosomes derived from quercetin-treated MSCs possessed enhanced anti-inflammatory and antioxidant properties.</p><p><strong>Conclusion: </strong>Collectively, our research underscores an optimized therapeutic strategy for IDD utilizing MSC-derived exosomes, thereby augmenting the efficacy of exosomes in intervertebral disc regeneration.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1061-1077"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767427","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":"Rapamycin Attenuates H₂O₂-Induced Oxidative Stress-Related Senescence in Human Skin Fibroblasts.","authors":"Yuyang Tang, Sen Yang, Zhen Qiu, Li Guan, Yigui Wang, Guixin Li, Yuanyu Tu, Lijuan Guo","doi":"10.1007/s13770-024-00660-2","DOIUrl":"10.1007/s13770-024-00660-2","url":null,"abstract":"<p><strong>Background: </strong>Oxidative stress plays an important role in the skin aging process. Rapamycin has been shown to have anti-aging effects, but its role in oxidative senescence of skin cells remains unclear. The aim of this study was to explore the effect of rapamycin on oxidative stress-induced skin cell senescence and to illustrate the mechanism.</p><p><strong>Methods: </strong>Primary human skin fibroblasts (HSFs) were extracted and a model of H₂O₂-induced oxidative senescence was constructed, and the effects of rapamycin on their value-added and migratory capacities were detected by CCK-8 and scratch assays. SA-β-gal was utilized to detect senescence, oxidatively closely related factors were also assessed. Gene and protein expressions of senescence, oxidative, and autophagy were detected by western blotting and quantitative-PCR. The data were analyzed by one-way analysis of variance.</p><p><strong>Results: </strong>Rapamycin (0.1 nmol/L for 48 h) promoted the proliferative and migration of H₂O₂-treated HSFs (p < 0.05), decreased senescent phenotypes SA-β-gal staining and the expression of P53, and MMP-1 proteins, and increased the expression level of COL1A-1 (p < 0.001). Rapamycin also enhanced the activities of SOD and HO-1, and effectively removed intracellular ROS, MDA levels (p < 0.05), in addition, autophagy-related proteins and genes were significantly elevated after rapamycin pretreatment (p < 0.001). Rapamycin upregulated the autophagy pathway to exert its protective effects.</p><p><strong>Conclusion: </strong>Our findings indicate that rapamycin shields HSFs from H₂O₂-induced oxidative damage, the mechanism is related to the reduction of intracellular peroxidation and upregulation of autophagy pathway. Therefore, rapamycin has the potential to be useful in the investigation and prevention of signs of aging and oxidative stress.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1049-1059"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876049","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}