Mark Dan Kirichenko

Transepithelial/transendothelial electrical resistance (TEER) is a label-free assay that is commonly used to assess tissue barrier integrity. TEER measurement systems have been embedded in organ-on-a-chip devices to provide live readouts of barrier functionality. Yet, these systems commonly provide the impedance values which correspond to the highest level of permeability throughout the chip and cannot provide localized information on specific regions of interest. This work introduces a system that provides this essential information: a spatial-TEER (S-TEER) organ-on-a-chip platform, which incorporates moving (scanning) electrodes that can measure electrical resistance at any desired location along the chip. We demonstrate the system's capacity to obtain localized measurements of permeability in selected regions of a cell sample. We show how, in a layer with non-uniform levels of cell coverage, permeability is higher in areas with lower cell density—suggesting that the system can be used to monitor local cellular growth in vitro. To demonstrate the applicability of the chip in studies of barrier function, we characterize tissue response to TNF-α and to EGTA, agents known to harm tissue barrier integrity.

Background: Air travel thrombosis continues to be a controversial topic. Exposure to hypoxia and hypobaric conditions during air travel is assumed a risk factor. The aim of this study is to explore changes in parameters of coagulation, fibrinolysis and blood flow in a rat model of exposure to hypobaric conditions that imitate commercial and combat flights. Methods: Sixty Sprague-Dawley male rats, aged 10 weeks, were divided into 5 groups according to the type and duration of exposure to hypobaric conditions. The exposure conditions were 609 m and 7620 m for 2 and 12 h duration. Blood count, thrombin– antithrombin complex, D-dimer, interleukin-1 and interleukin-6 were analyzed. All rats went through flight angiography MRI at day 13-post exposure. Results: No effect of the various exposure conditions was observed on coagulation, fibrinolytic system, IL-1 or IL-6. MRI angiography showed blood flow reduction in lower limb to less than 30% in 50% of the rats. The reduction in blood flow was more pronounced in the left vessel than in the right vessel (p = 0.006, Wilcoxon signed rank test). The extent of occlusion differed across exposure groups in the right, but not the left vessel (p = 0.002, p = 0.150, respectively, Kruskal-Wallis test). However, these differences did not correlate with the exposure conditions. Conclusion: In the present rat model, no clear correlation between various hypobaric conditions and activation of coagulation was observed. The reduction in blood flow in the lower limb also occurred in the control group and was not related to the type of exposure.

The human-relevance of an in vitro model is dependent on two main factors—(i) an appropriate human cell source and (ii) a modeling platform that recapitulates human in vivo conditions. Recent years have brought substantial advancements in both these aspects. In particular, mesenchymal stem cells (MSCs) have emerged as a promising cell source, as these cells can differentiate into multiple cell types, yet do not raise the ethical and practical concerns associated with other types of stem cells. In turn, advanced bioengineered in vitro models such as microfluidics, Organs-on-a-Chip, scaffolds, bioprinting and organoids are bringing researchers ever closer to mimicking complex in vivo environments, thereby overcoming some of the limitations of traditional 2D cell cultures. This review covers each of these advancements separately and discusses how the integration of MSCs into novel in vitro platforms may contribute enormously to clinical and fundamental research.