Engineering-inspired approaches to study β-cell function and diabetes

Abstract

Strategies to mitigate the pathologies from diabetes range from simply administering insulin to prescribing complex drug/biologic regimens combined with lifestyle changes. There is a substantial effort to better understand β-cell physiology during diabetes pathogenesis as a means to develop improved therapies. The convergence of multiple fields ranging from developmental biology to microfluidic engineering has led to the development of new experimental systems to better study complex aspects of diabetes and β-cell biology. Here we discuss the available insulin-secreting cell types used in research, ranging from primary human β-cells, to cell lines, to pluripotent stem cell-derived β-like cells. Each of these sources possess inherent strengths and weaknesses pertinent to specific applications, especially in the context of engineered platforms. We then outline how insulin-expressing cells have been used in engineered platforms and how recent advances allow for better mimicry of in vivo conditions. Chief among these conditions are β-cell interactions with other endocrine organs. This facet is beginning to be thoroughly addressed by the organ-on-a-chip community, but holds enormous potential in the development of novel diabetes therapeutics. Furthermore, high throughput strategies focused on studying β-cell biology, improving β-cell differentiation, or proliferation have led to enormous contributions in the field and will no doubt be instrumental in bringing new diabetes therapeutics to the clinic.

Islet-on-chip: promotion of islet health and functionviaencapsulation within a polymerizable fibrillar collagen scaffold

“…51,52 In general, multi-step fabrication methods have limited ease of use and reproducibility of microfluidic devices and prevented their widespread adoption and use by laboratories. 20,53,54 In this study, we sought to address the above-mentioned limitations by designing a novel 3D culture platform that recreates components of the in vivo microenvironment, namely physiologically relevant mass transport conditions and islet-ECM mechanochemical signaling. Previously, we have shown that islet encapsulation within fibrillar scaffolds prepared with polymerizable type I oligomeric collagen supports maintenance of islet morphology, viability, and function beyond 14 days in vitro in static culture conditions.…”

“…51,52 In general, multi-step fabrication methods have limited ease of use and reproducibility of microfluidic devices and prevented their widespread adoption and use by laboratories. 20,53,54…”

Employing Extracellular Matrix-Based Tissue Engineering Strategies for Age-Dependent Tissue Degenerations

“…Numerous stem cell therapy companies are attempting to engineer pancreatic tissues [149]. The pancreas is an organ of both the endocrine and exocrine systems, typically known for its role in controlling blood glucose levels.…”