In vitro models最新文献

{"title":"Macro- and micro-nutrient-based multiplex stress conditions modulate in vitro tumorigenesis and aggressive behavior of breast cancer spheroids.","authors":"Sukanya Gayan, Abhishek Teli, Anish Nair, Geetanjali Tomar, Tuli Dey","doi":"10.1007/s44164-021-00006-5","DOIUrl":"10.1007/s44164-021-00006-5","url":null,"abstract":"<p><strong>Purpose: </strong>The aggressive nature of a tumor is presumably its inherent one, but different environmental cues can manipulate it in many ways. In this context, the influence of metabolic stresses on tumor behavior needs to be analyzed to understand their far-reaching implications on tumor aggression and dormancy. This work investigates different facets of the tumor, such as tumorigenic capacity, tumor phenotype, and migration, under multiple metabolic stress conditions.</p><p><strong>Methods: </strong>Non-invasive and invasive multicellular spheroids (MTS) were created and subjected to multiple stress conditions, namely glucose, amino acid, and oxygen deprivation. Altered behavior of the MTS has been evaluated in the context of in vitro tumorigenesis, spheroid formation capacity, phenotype, mRNA profile, migration, and recruitment of mesenchymal stem cells.</p><p><strong>Results: </strong>The metabolic stress conditions were observed to negatively impact the in vitro tumorigenesis and spheroid formation process of invasive and non-invasive breast cancer cells. While the stress seemingly influences the growth and phenotype of spheroids, it does not alter the organization of sub-cellular entities significantly. Metabolic stress conditions impact the transcriptomic landscape of hypoxic, angiogenic, ECM deformation, glycolysis shift, and protein starvation-related gene clusters. MTSs do not adhere or migrate under stress, but they exhibit different modalities of migration when rescued. Invasive spheroids, after the rescue, exhibit increased aggressiveness. Furthermore, stressed spheroid was observed to control the migration and recruitment of mesenchymal stem cells.</p><p><strong>Conclusion: </strong>Multiplex metabolic stresses could control the tumorigenesis while influencing the physiology of invasive and non-invasive breast cancer spheroids along with their migration pattern and tumor-stromal crosstalk.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s44164-021-00006-5.</p>","PeriodicalId":73357,"journal":{"name":"In vitro models","volume":"2 1","pages":"85-101"},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88955873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A vascularized bone-on-a-chip model development via exploring mechanical stimulation for evaluation of fracture healing therapeutics.","authors":"Bodhisatwa Das, Sundeep V Seesala, Pallabi Pal, Trina Roy, Preetam Guha Roy, Santanu Dhara","doi":"10.1007/s44164-021-00004-7","DOIUrl":"10.1007/s44164-021-00004-7","url":null,"abstract":"<p><p>Bone is the major connective tissue maintaining the structural integrity of the human body. However, fracture and many skeletal degenerative diseases can compromise this function. Thus, therapeutics related to bone degeneration are of significant research interest and require good in vitro models for such therapeutic evaluation. Bone is a highly vascularized tissue and incorporation of this feature is significantly important for mimicking the osteogenic microenvironment. In the current study, we developed a vascularized flat bone model via simultaneous mechanical actuation of mechanical strain and fluid shear. The mechanical strain was achieved by static magnetic field actuation of a magnetic nanocomposite scaffold. The fluid shear was generated by developing a micropattern on the magnetic nanocomposite via replica molding and laser-based microfabrication. From the live cell imaging window of the microdevice, both bone and vasculature like cellular morphology was observed. The SEM study showed thick ECM deposition in the dynamic culture. In the PCR study, both osteogenic (Col-1, osteocalcin) and angiogenic phenotypes (PECAM) were observed in the dynamic culture scaffolds while chondrogenic marker (Col-2) was downregulated.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s44164-021-00004-7.</p>","PeriodicalId":73357,"journal":{"name":"In vitro models","volume":"50 1","pages":"73-83"},"PeriodicalIF":0.0,"publicationDate":"2021-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75751244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ex vivo evaluation of blood coagulation on endothelial glycocalyx-inspired surfaces using thromboelastography.","authors":"Yanyi Zang, Jessi R Vlcek, Jamie Cuchiaro, Ketul C Popat, Christine S Olver, Matt J Kipper, Melissa M Reynolds","doi":"10.1007/s44164-021-00001-w","DOIUrl":"10.1007/s44164-021-00001-w","url":null,"abstract":"<p><strong>Purpose: </strong>Present blood-contacting materials have not yet demonstrated to be effective in reducing blood coagulation without causing additional side effects clinically. We have developed an endothelial glycocalyx-inspired biomimetic surface that combines nanotopography, heparin presentation, and nitric oxide (NO)-releasing features. The resulting modified surfaces have already shown promise in reducing unfavorable blood-material interactions using platelet-rich plasma. In this study, the efficacy of modified surfaces for reducing coagulation of human whole blood was measured. In addition, the effects of leached polysaccharides and chemical modification of the modified surfaces were evaluated.</p><p><strong>Methods: </strong>Leached polysaccharides in the incubation solution were detected by a refractive index method to determine the potential influences of these modified surfaces on the blood coagulation observation. Chemical modifications by the nitrosation process on the polysaccharides in the modified surfaces were detected using attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). Clot formation parameters were measured using thromboelastography (TEG), a clinically relevant technique to evaluate whole blood coagulation.</p><p><strong>Results: </strong>No polysaccharides were detected in the heparinized polyelectrolyte multilayer-coated titania nanotube array surface (TiO₂NT + PEM) incubation solution; however, polysaccharides were detected from NO-releasing TiO₂NT + PEM surface (TiO₂NT + PEM + NO) incubation solution both after the nitrosation process and after all NO was released. The structures of thiolated chitosan and heparin were altered by <i>t</i>-butyl nitrite. All heparin-containing surfaces were shown to slow or inhibit clot formation.</p><p><strong>Conclusion: </strong>This study is the first to evaluate these endothelial glycocalyx-inspired surfaces using clinically relevant parameters, as well as proposing potential influences of these modified surfaces on the inhibition of clot formation.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s44164-021-00001-w.</p>","PeriodicalId":73357,"journal":{"name":"In vitro models","volume":"5 1","pages":"59-71"},"PeriodicalIF":0.0,"publicationDate":"2021-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89546624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Welcome to <i>In vitro models</i>.","authors":"J Miguel Oliveira, Ketul C Popat","doi":"10.1007/s44164-021-00002-9","DOIUrl":"10.1007/s44164-021-00002-9","url":null,"abstract":"","PeriodicalId":73357,"journal":{"name":"In vitro models","volume":"2011 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2021-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73353881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}