Tissue Barriers最新文献

The maintenance of body homeostasis relies heavily on physiological barriers. Dysfunction of these barriers can lead to various pathological processes, including increased exposure to toxic materials and microorganisms. Various methods exist to investigate barrier function in vivo and in vitro. To investigate barrier function in a highly reproducible manner, ethically, and high throughput, researchers have turned to non-animal techniques and micro-scale technologies. In this comprehensive review, the authors summarize the current applications of organ-on-a-chip microfluidic devices in the study of physiological barriers. The review covers the blood-brain barrier, ocular barriers, dermal barrier, respiratory barriers, intestinal, hepatobiliary, and renal/bladder barriers under both healthy and pathological conditions. The article then briefly presents placental/vaginal, and tumour/multi-organ barriers in organ-on-a-chip devices. Finally, the review discusses Computational Fluid Dynamics in microfluidic systems that integrate biological barriers. This article provides a concise yet informative overview of the current state-of-the-art in barrier studies using microfluidic devices.

The development of novel strategies to counteract diseases related to barrier dysfunction is a priority, since sepsis and acute respiratory distress syndrome are still associated with high mortality rates. In the present study, we focus on the effects of the unfolded protein response suppressor (UPR) 4-Phenylbutyrate (4-PBA) in Lipopolysaccharides (LPS)-induced endothelial injury, to investigate the effects of that compound in the corresponding damage. 4-PBA suppressed binding immunoglobulin protein (BiP) - a UPR activation marker - and potentiated LPS - induced signal transducer and activator of transcription 3 (STAT3) and extracellular signal‑regulated protein kinase (ERK) 1/2 activation. In addition to those effects, 4-PBA enhanced paracellular hyperpermeability in inflamed bovine pulmonary endothelial cells, and did not affect cell viability in moderate concentrations. Our observations suggest that UPR suppression due to 4-PBA augments LPS-induced endothelial injury, as well as the corresponding barrier disruption.

Intestinal organoid technology has revolutionized our approach to in vitro cell culture due in part to their three-dimensional structures being more like the native tissue from which they were derived with respect to cellular composition and architecture. For this reason, organoids are becoming the new gold standard for undertaking intestinal epithelial cell research. Unfortunately, their otherwise advantageous three-dimensional geometry prevents easy access to the apical epithelium, which is a major limitation when studying interactions between dietary or microbial components and host tissues. To overcome this problem, we developed porcine colonoid-derived monolayers cultured on both permeable Transwell inserts and tissue culture treated polystyrene plates. We found that seeding density and culture format altered the expression of genes encoding markers of specific cell types (stem cells, colonocytes, goblets, and enteroendocrine cells), and barrier maturation (tight junctions). Additionally, we found that changes to the formulation of the culture medium altered the cellular composition of colonoids and of monolayers derived from them, resulting in cultures with an increasingly differentiated phenotype that was similar to that of their tissue of origin.

Kidney disease is a devastating condition affecting millions of people worldwide, where over 100,000 patients in the United States alone remain waiting for a lifesaving organ transplant. Concomitant with a surge in personalized medicine, single-gene mutations, and polygenic risk alleles have been brought to the forefront as core causes of a spectrum of renal disorders. With the increasing prevalence of kidney disease, it is imperative to make substantial strides in the field of kidney genetics. Nephrons, the core functional units of the kidney, are epithelial tubules that act as gatekeepers of body homeostasis by absorbing and secreting ions, water, and small molecules to filter the blood. Each nephron contains a series of proximal and distal segments with explicit metabolic functions. The embryonic zebrafish provides an ideal platform to systematically dissect the genetic cues governing kidney development. Here, we review the use of zebrafish to discover nephrogenesis genes.

Exosomes are membrane-bound micro-vesicles that possess endless therapeutic potential for treatment of numerous pathologies including autoimmune, cardiovascular, ocular, and nervous disorders. Despite considerable knowledge about exosome biogenesis and secretion, still, there is a lack of information regarding exosome uptake by cell types and internal signaling pathways through which these exosomes process cellular response. Exosomes are key components of cell signaling and intercellular communication. In central nervous system (CNS), exosomes can penetrate BBB and maintain homeostasis by myelin sheath regulation and the waste products elimination. Therefore, the current review summarizes role of exosomes and their use as biomarkers in cardiovascular, nervous and ocular disorders. This aspect of exosomes provides positive hope to monitor disease development and enable early diagnosis and treatment optimization. In this review, we have summarized recent findings on physiological and therapeutic effects of exosomes and also attempt to provide insights about stress-preconditioned exosomes and stem cell-derived exosomes.

We aim to construct a three-dimensional nano-skin scaffold material in vitro and study its promoting effect on wound healing in vivo. In this study, hybrid constructs of three-dimensional (3D) scaffolds were successfully fabricated by combination of type I collagen (COL-1) and polylactic-glycolic acid (PLGA). Fibroblasts and human umbilical cord mesenchymal stem cells (hUCMSCs) were used to implanted into 3D scaffolds and constructed into SD skin scaffolds in vitro. Finally, the fibroblasts/scaffolds complexes were inoculated on the surface of rat wound skin to study the promoting effect of the complex on wound healing. In our study, we successfully built a 3D scaffold, which had a certain porosity. Meanwhile, the content of COL-1 in the cell supernatant of fibroblast/scaffold complexes was increased. Furthermore, the expression of F-actin, CD105, integrin β, VEGF, and COL-1 was up-regulated in hUCMSC/scaffold complexes compared with the control group. In vivo, fibroblast/scaffold complexes promoted wound healing in rats. Our data suggested that the collagen Ⅳ and vimentin were elevated and collagen fibers were neatly arranged in the fibroblast/scaffold complex group was significantly higher than that in the scaffold group. Taken together, fibroblast/scaffold complexes were expected to be novel materials for treating skin defects.

Claudin-2-dependent pore function mediates paracellular cation permeability and can result in pathogenesis of many diseases. Although existing various types of claudins, including barrier-forming and pore-forming claudins, their heterodimeric interaction affecting barrier and pore functions has never been fully elucidated yet. Recently, Shashikanth and colleagues demonstrated that expression of claudin-4 was able to antagonize paracellular pore activity of claudin-2. This commentary will emphasize the mechanism underlying claudin-4-mediated claudin-2-dependent pore inhibition and discuss its potential therapeutic and prognostic applications.

Inflammatory bowel diseases (IBDs) are chronic conditions in which the digestive tract undergoes cycles of relapsing and remitting inflammatory episodes that cause patients to experience severe abdominal pain, bleeding, and diarrhea. Developing noninvasive and cost-effective surveillance methods that can detect an ensuing disease bout proffers an avenue to improve the quality of life for patients with IBD. Now, a recent report describes an ingenious, economical approach using a rationally designed Escherichia coli strain that can dynamically monitor inflammation inside the mammalian gastrointestinal tract. The ability of the engineered probiotic to specifically discern between dormant and activated inflammatory states of the digestive system demonstrates that living biosensors can be used to monitor health status, thus providing a powerful proof of concept that heralds the arrival of a new age of clinical diagnostics for people living with inflammatory diseases of the gut.

Cardiovascular diseases are a significant global health challenge and pervasive cause of mortality worldwide. Heart failure due to cardiovascular disease is characterized by the inability of the heart to pump blood efficiently to meet the metabolic demands of the body. The pathophysiology of heart failure involves myocardial remodeling due to excessive deposition of extracellular matrix proteins by cardiac myofibroblasts - structural changes which impair contractility, reduce compliance, and ultimately reduce stroke volume. Now, a recent report has uncovered an essential role for Iroquois homeobox 2 in the transcriptional regulation of cardiac fibrosis, illuminating new mechanistic insights that can be applied to developing future clinical therapies.

The fungus Cryptococcus neoformans is pervasive in our environment and causes the infectious disease cryptococcosis in humans, most commonly in immunocompromised patients. In addition to corroborating the avian origins of a case of cryptococcosis in an immunocompromised patient in 2000, a fascinating recent report has now characterized the genetic and phenotypic changes that occur in this C. neoformans during passage in mammalian hosts. Interestingly, mouse-passaged isolates showed differences in virulence factors ranging from capsule size, melanization, nonlytic macrophage exocytosis, and amoeba predation resistance as compared to the patient strain. Taken together, these results provide new insights about the relationship between mutations acquired during an infection and changes in virulence.