Spatial trans-epithelial electrical resistance (S-TEER) integrated in organs-on-chips.

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.

Mesenchymal Stem Cells as a Promising Cell Source for Integration in Novel In Vitro Models.

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.