Pancreas-on-a-Chip Technology for Transplantation Applications

Human pancreas-on-a-chip (PoC) technology is quickly advancing as a platform for complex in vitro modeling of islet physiology. This review summarizes the current progress and evaluates the possibility of using this technology for clinical islet transplantation.

PoC microfluidic platforms have mainly shown proof of principle for long-term culturing of islets to study islet function in a standardized format. Advancement in microfluidic design by using imaging-compatible biomaterials and biosensor technology might provide a novel future tool for predicting islet transplantation outcome. Progress in combining islets with other tissue types gives a possibility to study diabetic interventions in a minimal equivalent in vitro environment.

For islet transplantation, existing procedures involve isolation and purification of the islets from the rest of the pancreatic tissue which often leads to ischemic damage and a pro-inflammatory signature. Prior to transplantation, islet quality is evaluated mainly by measurements of number of islets, sterility, purity, and viability. Depending on the release criteria at different centers, this also includes potency assays such as static or dynamic glucose-stimulated insulin secretion followed by a calculation of the stimulation index (SI). Commonly, SI > 1 is considered as enough evidence for a sufficient response of the isolated islets to blood glucose. Unfortunately, this test does not necessarily correlate with the clinical outcome after islet transplantation, probably due to a variability of in vitro environmental factors.

While in vitro differentiation of stem cells to beta-like cells is slowly improving, awareness about the importance of the micro-environment of the beta cells and its standardized supply of oxygen, nutrition, and other factors is raising. Hence, platforms that provide a controlled micro-environment and enable rigid standardization of surrounding conditions are being developed.

Pancreas-on-a-chip (PoC), which refers mainly to the study of endocrine part of the pancreas on microfluidic chip, may be used as a standardized and real-time assessment platform for evaluating islet potency and quality. Organ-on-a-chip (OoC) technology, in general, promises to provide a test and interrogation environment that might replace the complexity of an animal model. OoC is a microfluidic-based device enabling to culture and grow living cells and organoid substructures in a controlled micro-environment. Commonly, OoC platforms recapitulate one or more aspects of the organ’s dynamics, functionality, and in vivo (patho) physiological responses under real-time monitoring of different cultured tissue types.

OoC-based systems have the potential to be used for a range of applications such as personalized organ function and dysfunction, as well as pharmacological interventions that are particularly difficult to study in an isolated 2D or 3D in vitro laboratory setting. PoC devices that enable in a minimal equivalent environment to mimic the function of islets in particular may enable us to gain new information on the islet physiology and the impact of therapeutic interventions. Importantly, PoC technology also promises to advance standardization and quality control of the islets or stem cell-derived beta-like cells per se for replacement therapy. In this review, we will present the various developments toward PoC platforms and discuss the use of this technology for clinical transplantation.