Tissue BarriersPub Date : 2024-11-07DOI: 10.1080/21688370.2024.2424628
Apoorva, Atul Kumar, Sunit K Singh
{"title":"Dengue virus NS1 hits hard at the barrier integrity of human cerebral microvascular endothelial cells via cellular microRNA dysregulations.","authors":"Apoorva, Atul Kumar, Sunit K Singh","doi":"10.1080/21688370.2024.2424628","DOIUrl":"https://doi.org/10.1080/21688370.2024.2424628","url":null,"abstract":"<p><p>Dengue virus (DENV) infections are commonly reported in the tropical and subtropical regions of the world. DENV is reported to exploit various strategies to cross the blood-brain barrier. The NS1 protein of DENV plays an important role in viral neuropathogenesis, resulting in endothelial hyperpermeability and cytokine-induced vascular leak. miRNAs are short non-coding RNAs that play an important role in post-transcriptional gene regulations. However, no comprehensive information about the involvement of miRNAs in DENV-NS1-mediated neuropathogenesis has been explored to date. We observed that DENV-NS1 significantly alters the cellular miRNome of human cerebral microvascular endothelial cells in a bystander fashion. Subsequent target prediction and pathway enrichment analysis indicated that these microRNAs and their corresponding target genes are involved in pathways associated with blood-brain barrier dysfunction such as \"Adherens junction\" and \"Tight junction\". Additionally, several miRNA-mRNA pairs were also found to be involved in cellular signaling pathways related to cytokine production, for instance, \"Jak-STAT signaling pathway\", \"Chemokine signaling pathway\", \"IL-17 signaling pathway\", \"NF-κB signaling pathway\", and \"Viral protein interaction with cytokine and cytokine receptor\". The dysregulated production of inflammatory cytokines is reported to compromise BBB permeability. This study is the first report to demonstrate that DENV-NS1-mediated miRNA perturbations are crucial in compromising endothelial barrier integrity. It also offers insights into potential therapeutic targets to mitigate DENV-NS1-induced vascular permeability and inflammation.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2424628"},"PeriodicalIF":3.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tissue BarriersPub Date : 2024-11-05DOI: 10.1080/21688370.2024.2423137
Snezhanna Medvedeva, Kseniya Achasova, Lidiya Boldyreva, Anna Ogienko, Elena Kozhevnikova
{"title":"The application of explants, crypts, and organoids as models in intestinal barrier research.","authors":"Snezhanna Medvedeva, Kseniya Achasova, Lidiya Boldyreva, Anna Ogienko, Elena Kozhevnikova","doi":"10.1080/21688370.2024.2423137","DOIUrl":"https://doi.org/10.1080/21688370.2024.2423137","url":null,"abstract":"<p><p><i>In vitro</i> models are of great importance in advancing our understanding of human diseases, especially complex disorders with unknown etiologies like inflammatory bowel diseases (IBD). One of the key IBD features is the increased intestinal permeability. The disruption of the intestinal barrier can occur due to a destructive inflammatory response involving intestinal cell death. Alternatively, proteins that form tight junctions (TJ) fail to form function complexes and promote epithelial barrier disruption. The mechanisms behind this process are not fully understood. Thus, <i>in vitro</i> models that facilitate studying the intestinal barrier and its molecular components are of particular importance in the context of IBD. There are <i>in vitro</i> and <i>ex vivo</i> models that can be used to recapitulate some aspects of IBD. Among these are intestinal explants, crypts, and epithelial 3D-organoids. Here we describe some practical limitations of isolated crypts, gut tissue explants, and intestinal organoids as models in epithelial barrier biology, and TJ in particular. Our findings demonstrate that only 3D intestinal organoids formed from single cells are suitable to study barrier permeability <i>in vitro</i>, as primary crypt-derived organoids do not retain epithelial integrity due to cell death. Importantly, 3D organoids raised in culture conditions may fail to recapitulate inflammatory and barrier phenotypes of the source mouse model. To study the features of the inflamed epithelium, <i>ex vivo</i> intestinal explants and crypts were employed. We show here that isolated crypts do not preserve native TJ structure in a long-term experimental setting and tend to disintegrate in the unsupported culture environment. However, intestinal explants were stable in culture conditions for about 24 hours and demonstrated their applicability for short-term living tissue imaging and fluorescence recovery after photobleaching (FRAP). Thus, a combination of 3D organoids and intestinal explants provides a more accurate experimental platform to understand the intestinal epithelial barrier.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2423137"},"PeriodicalIF":3.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tissue BarriersPub Date : 2024-10-01Epub Date: 2023-12-12DOI: 10.1080/21688370.2023.2292463
Li Ai, Chen Xin, Muhammad Usman, Yu Zhu, Hong Lu
{"title":"Effect of Bevacizumab on traumatic penumbra brain edema in rats at different time points.","authors":"Li Ai, Chen Xin, Muhammad Usman, Yu Zhu, Hong Lu","doi":"10.1080/21688370.2023.2292463","DOIUrl":"10.1080/21688370.2023.2292463","url":null,"abstract":"<p><p>Traumatic penumbra (TP) is a secondary injury area located around the core area of traumatic brain injury after brain trauma, and is an important factor affecting the outcome of traumatic brain injury (TBI). The main pathological change caused by TP is brain edema, including (cellular brain edema and vascular brain edema). The formation and development of brain edema in the TP area are closely related to the blood-brain barrier (BBB) and vascular endothelial growth factor (VEGF). VEGF is a vascular permeability factor that can promote angiogenesis and increase BBB permeability, and there is a debate on the pros and cons of its role in early TBI. Therefore, in the early stage of TBI, when using the VEGF inhibitor bevacizumab to treat TP area brain edema, the timing of bevacizumab administration is particularly important, and there are currently no relevant literature reports. This article explores the treatment time window and optimal treatment time point of bevacizumab in the treatment of cerebral edema in the TP area by administering the same dose of bevacizumab at different time points after brain injury in rats. The results showed that there was traumatic brain edema in TP area, BBB structure and function were damaged, VEGF expression and angiogenesis were increased. Compared with TBI + NS Group, after Bevacizumab treatment, brain edema in TP area was alleviated, BBB structure and function were improved, VEGF expression and angiogenesis were decreased in each treatment group, and the effect of TBI + Bevacizumab 1 h group was the most significant. Bevacizumab can be used as a targeted therapy for traumatic brain edema. The therapeutic time window of bevacizumab for traumatic brain edema is within 12 hours after TBI, and 1 h is the optimal therapeutic time point.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2292463"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138809824","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}
Tissue BarriersPub Date : 2024-10-01Epub Date: 2023-12-05DOI: 10.1080/21688370.2023.2290946
Elysa Ng May May, Rebecca A Wingert
{"title":"The amazing axolotl: robust kidney regeneration following acute kidney injury.","authors":"Elysa Ng May May, Rebecca A Wingert","doi":"10.1080/21688370.2023.2290946","DOIUrl":"10.1080/21688370.2023.2290946","url":null,"abstract":"<p><p>The incidence of kidney disease from acute and chronic conditions continues to escalate worldwide. Interventions to replace renal function after organ failure remain limited to dialysis or transplantation, as human kidneys exhibit a limited capacity to repair damaged cells or regenerate new ones. In contrast, animals ranging from flies to fishes and even some mammals like the spiny mouse exhibit innate abilities to regenerate their kidney cells following injury. Now, a recent study has illuminated how the Mexican salamander, <i>Ambystoma mexicanum</i>, most commonly known as the axolotl, possesses a kidney with remarkable similarity to humans, which can robustly regenerate following acute chemical damage. These discoveries position the axolotl as a new model that can be used to advance our understanding about the fundamental mechanisms of kidney regeneration.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2290946"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488540","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}
Tissue BarriersPub Date : 2024-10-01Epub Date: 2023-12-14DOI: 10.1080/21688370.2023.2292461
Elizabeth M Rhea, Alice Babin, Peter Thomas, Mohamed Omer, Riley Weaver, Kim Hansen, William A Banks, Konrad Talbot
{"title":"Brain uptake pharmacokinetics of albiglutide, dulaglutide, tirzepatide, and DA5-CH in the search for new treatments of Alzheimer's and Parkinson's diseases.","authors":"Elizabeth M Rhea, Alice Babin, Peter Thomas, Mohamed Omer, Riley Weaver, Kim Hansen, William A Banks, Konrad Talbot","doi":"10.1080/21688370.2023.2292461","DOIUrl":"10.1080/21688370.2023.2292461","url":null,"abstract":"<p><strong>Background: </strong>A number of peptide incretin receptor agonists (IRAs) show promise as therapeutics for Alzheimer's disease (AD) and Parkinson's disease (PD). Transport across the blood-brain barrier (BBB) is one way for IRAs to act directly within the brain. To determine which IRAs are high priority candidates for treating these disorders, we have studied their brain uptake pharmacokinetics.</p><p><strong>Methods: </strong>We quantitatively measure the ability of four IRAs to cross the BBB. We injected adult male CD-1 mice intravenously with <sup>125</sup>I- or <sup>14</sup>C-labeled albiglutide, dulaglutide, DA5-CH, or tirzepatide and used multiple-time regression analyses to measure brain kinetics up to 1 hour. For those IRAs failing to enter the brain 1 h after intravenous injection, we also investigated their ability to enter over a longer time frame (i.e., 6 h).</p><p><strong>Results: </strong>Albiglutide and dulaglutide had the fastest brain uptake rates within 1 hour. DA5-CH appears to enter the brain rapidly, reaching equilibrium quickly. Tirzepatide does not appear to cross the BBB within 1 h after iv injection but like albumin, did so slowly over 6 h, presumably via the extracellular pathways.</p><p><strong>Conclusions: </strong>We find that IRAs can cross the BBB by two separate processes; one that is fast and one that is slow. Three of the four IRAs investigated here have fast rates of transport and should be taken into consideration for testing as AD and PD therapeutics as they would have the ability to act quickly and directly on the brain as a whole.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2292461"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138809805","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}
Tissue BarriersPub Date : 2024-10-01Epub Date: 2024-01-28DOI: 10.1080/21688370.2024.2309025
Sophia Baker, Thanh Khoa Nguyen, Rebecca A Wingert
{"title":"Tails of nephron ciliated cell development: insights on patterning a functional tissue barrier from the zebrafish.","authors":"Sophia Baker, Thanh Khoa Nguyen, Rebecca A Wingert","doi":"10.1080/21688370.2024.2309025","DOIUrl":"10.1080/21688370.2024.2309025","url":null,"abstract":"<p><p>Cilia are hair-like structures found on the surface of nearly all vertebrate cell types where they have central roles in regulating development and orchestrating physiological events. There is growing interest in understanding the mechanisms of ciliogenesis due to the profound consequences that follow from the absence of proper ciliary function, which include diseases that affect the renal, respiratory, reproductive, nervous, visual, and digestive systems, among others. Now, a recent report has discerned new roles for the transcription factor <i>estrogen-related receptor gamma a</i> (<i>esrrγa)</i> in ciliated cell ontogeny within the embryonic zebrafish kidney and other tissues. Further, the team of researchers discovered that genetic ablation of murine homolog ERRγ in adult kidney epithelial cells led to shortened cilia, which precedes cystogenesis. These intriguing findings expand our fundamental understanding of the pathological basis of cilia defects, which is relevant for identifying future therapeutic targets for ciliopathies.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2309025"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139571381","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}
Tissue BarriersPub Date : 2024-10-01Epub Date: 2023-12-07DOI: 10.1080/21688370.2023.2289838
Paola Bendinelli, Ivano De Noni, Stefano Cattaneo, Tiziana Silvetti, Milena Brasca, Federica Piazzalunga, Elena Donetti, Anita Ferraretto
{"title":"Surface layer proteins from <i>Lactobacillus helveticus</i> ATCC® 15009™ affect the gut barrier morphology and function.","authors":"Paola Bendinelli, Ivano De Noni, Stefano Cattaneo, Tiziana Silvetti, Milena Brasca, Federica Piazzalunga, Elena Donetti, Anita Ferraretto","doi":"10.1080/21688370.2023.2289838","DOIUrl":"10.1080/21688370.2023.2289838","url":null,"abstract":"<p><p>Paraprobiotics and postbiotics represent a valid alternative to probiotic strains for ameliorating and preserving a healthy intestinal epithelial barrier (IEB). The present study investigated the effects of surface layer proteins (S-layer) of the dairy strain <i>Lactobacillus helveticus</i> ATCC® 15009™ (<i>Lb</i> ATCC® 15009™), as paraprobiotic, on the morpho-functional modulation of IEB in comparison to live or heat-inactivated <i>Lb</i> ATCC® 15009™ in an <i>in vitro</i> co-culture of Caco-2/HT-29 70/30 cells. Live or heat-inactivated <i>Lb</i> ATCC® 15009™ negatively affected transepithelial electrical resistance (TEER) and paracellular permeability, and impaired the distribution of Claudin-1, a tight junction (TJ) transmembrane protein, as detected by immunofluorescence (IF). Conversely, the addition of the S-layer improved TEER and decreased permeability in physiological conditions in co-cultures with basal TEER lower than 50 ohmcm<sup>2</sup>, indicative of a more permeable physiological IEB known as leaky gut. Transmission electron microscopy (TEM) and IF analyses suggested that the S-layer induces a structural TJ rearrangement and desmosomes' formation. S-layer also restored TEER and permeability in the presence of LPS, but not of a mixture of pro-inflammatory cytokines (TNF-α plus IFN-γ). IF analyses showed an increase in Claudin-1 staining when LPS and S-layer were co-administered with respect to LPS alone; in addition, the S-layer counteracted the reduction of alkaline phosphatase detoxification activity and the enhancement of pro-inflammatory interleukin-8 release both induced by LPS. Altogether, these data corroborate a paraprobiotic role of S-layer from <i>Lb</i> ATCC® 15009™ as a possible candidate for therapeutic and prophylactic uses in conditions related to gastrointestinal health and correlated with extra-intestinal disorders.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2289838"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138499484","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}
Tissue BarriersPub Date : 2024-10-01Epub Date: 2024-01-16DOI: 10.1080/21688370.2024.2301799
Kursad Turksen
{"title":"Tissue barriers and their impact.","authors":"Kursad Turksen","doi":"10.1080/21688370.2024.2301799","DOIUrl":"10.1080/21688370.2024.2301799","url":null,"abstract":"","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2301799"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139472187","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":"Decellularized small intestine scaffolds: a potential xenograft for restoration of intestinal perforation.","authors":"Kishor Tardalkar, Sonal Patil, Leena Chaudhari, Jeevitaa Kshersagar, Mrunal Damle, Akshay Kawale, Nilesh Bhamare, Vaishnavi Desai, Narayani Pathak, Vaishali Gaikwad, Meghnad G Joshi","doi":"10.1080/21688370.2023.2290940","DOIUrl":"10.1080/21688370.2023.2290940","url":null,"abstract":"<p><p>Small intestine perforation is a serious medical condition that requires immediate medical attention. The traditional course of treatment entails resection followed by anastomosis; however, it has complications such as small bowel syndrome (SBS), anastomotic leakage, and fistula formation. Here, a novel strategy is demonstrated, that utilizes the xenogeneic, decellularized goat small intestine as a patch for small intestine regeneration in cases of intestinal perforation. The goat small intestine scaffold underwent sodium dodecyl sulfate decellularization, which revealed consistent, quick, and effective decellularization. Decellularization contributed the least amount of extracellular matrix degradation while maintaining the intestinal architecture. By implanting the decellularized goat small intestine scaffolds (DGSIS) on the chorioallantoic membrane (CAM), no discernible loss of angiogenesis was seen in the CAM region, and this enabled the DGSIS to be evaluated for biocompatibility <i>in ovo</i>. The DGSIS was then xeno-transplanted as a patch on a small intestine perforation rat model. After 30 days post transplant, barium salt used as contrast gastrointestinal X-ray imaging revealed no leakage or obstruction in the small intestine. Histology, scanning electron microscopy, and immunohistochemistry assisted in analyzing the engraftment of host cells into the xeno patch. The xeno-patch expressed high levels of E-cadherin, α-smooth muscle actin (α-SMA), Occludin, Zonnula occluden (ZO-1), Ki 67, and Na<sup>+</sup>/K<sup>+</sup>-ATPase. The xeno-patch was consequently recellularized and incorporated into the host without causing an inflammatory reaction. As an outcome, decellularized goat small intestine was employed as a xenograft and could be suitable for regeneration of the perforated small intestine.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2290940"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488539","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}
Tissue BarriersPub Date : 2024-10-01Epub Date: 2024-02-12DOI: 10.1080/21688370.2024.2315702
Hoang-Tuan Nguyen, Siiri-Liisa Rissanen, Mimosa Peltokangas, Tino Laakkonen, Jere Kettunen, Lara Barthod, Ragul Sivakumar, Anniina Palojärvi, Pauliina Junttila, Jussi Talvitie, Michele Bassis, Sarah L Nickels, Sara Kalvala, Polina Ilina, Päivi Tammela, Sarka Lehtonen, Jens C Schwamborn, Sebastien Mosser, Prateek Singh
{"title":"Highly scalable and standardized organ-on-chip platform with TEER for biological barrier modeling.","authors":"Hoang-Tuan Nguyen, Siiri-Liisa Rissanen, Mimosa Peltokangas, Tino Laakkonen, Jere Kettunen, Lara Barthod, Ragul Sivakumar, Anniina Palojärvi, Pauliina Junttila, Jussi Talvitie, Michele Bassis, Sarah L Nickels, Sara Kalvala, Polina Ilina, Päivi Tammela, Sarka Lehtonen, Jens C Schwamborn, Sebastien Mosser, Prateek Singh","doi":"10.1080/21688370.2024.2315702","DOIUrl":"10.1080/21688370.2024.2315702","url":null,"abstract":"<p><p>The development of new therapies is hampered by the lack of predictive, and patient-relevant in vitro models. Organ-on-chip (OOC) technologies can potentially recreate physiological features and hold great promise for tissue and disease modeling. However, the non-standardized design of these chips and perfusion control systems has been a barrier to quantitative high-throughput screening (HTS). Here we present a scalable OOC microfluidic platform for applied kinetic in vitro assays (AKITA) that is applicable for high, medium, and low throughput. Its standard 96-well plate and 384-well plate layouts ensure compatibility with existing laboratory workflows and high-throughput data collection and analysis tools. The AKITA plate is optimized for the modeling of vascularized biological barriers, primarily the blood-brain barrier, skin, and lung, with precise flow control on a custom rocker. The integration of trans-epithelial electrical resistance (TEER) sensors allows rapid and repeated monitoring of barrier integrity over long time periods. Together with automated liquid handling and compound permeability testing analyses, we demonstrate the flexibility of the AKITA platform for establishing human-relevant models for preclinical drug and precision medicine's efficacy, toxicity, and permeability under near-physiological conditions.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2315702"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724198","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}