New Frontiers in Three-Dimensional Culture Platforms to Improve Diabetes Research

Abstract

Diabetes mellitus is associated with defects in islet β-cell functioning and consequent hyperglycemia resulting in multi-organ damage. Physiologically relevant models that mimic human diabetic progression are urgently needed to identify new drug targets. Three-dimensional (3D) cell-culture systems are gaining a considerable interest in diabetic disease modelling and are being utilized as platforms for diabetic drug discovery and pancreatic tissue engineering. Three-dimensional models offer a marked advantage in obtaining physiologically relevant information and improve drug selectivity over conventional 2D (two-dimensional) cultures and rodent models. Indeed, recent evidence persuasively supports the adoption of appropriate 3D cell technology in β-cell cultivation. This review article provides a considerably updated view of the benefits of employing 3D models in the experimental workflow compared to conventional animal and 2D models. We compile the latest innovations in this field and discuss the various strategies used to generate 3D culture models in diabetic research. We also critically review the advantages and the limitations of each 3D technology, with particular attention to the maintenance of β-cell morphology, functionality, and intercellular crosstalk. Furthermore, we emphasize the scope of improvement needed in the 3D culture systems employed in diabetes research and the promises they hold as excellent research platforms in managing diabetes.

Advances in the application of extracellular vesicles derived from three-dimensional culture of stem cells

“…Scaffold-free 3D cell culture is where cells self-assemble to form spheroids in the absence of scaffolds [ 89 ]. The major ones include forced floating, hanging drop, magnetic levitation and stirring spinner flask culture.…”

“…The forced floating method primarily uses ultra-low attachment plates, which are usually treated with hydrophilic or hydrophobic coatings, or agarose, to prevent cell adhesion to the substrate, promoting spheroid formation [ 90 , 91 ]. Although this method is simple and easy to execute, it cannot control the number of cells per spheroid and is not easy to repeat [ 89 ]. The hanging drop method eliminates surface attachment by placing cell suspensions in droplets at the underside of petri dish lids, where gravity induces cell aggregation at the bottom of the droplets to form spheroids [ 92 , 93 ].…”

Cell identity dynamics and insight into insulin secretagogues when employing stem cell-derived islets for disease modeling

“…Primary human islets isolated from deceased pancreas donors provide invaluable experimental material. However, its widespread usage is hindered by limited availability, donor variability, relative short viability in culture, heterogeneity, and ethical and regulatory considerations ( Mohandas et al, 2023 ). Pancreatic tissue slices enable study of human islet cell physiology at the cellular to multi-islet level.…”