Pancreatic islet transplantation is performed as a potential treatment for type 1 diabetes mellitus. However, this approach is significantly limited due to the critical shortage of islet sources. Recently, a number of publications have developed protocols for directed β-cell differentiation of pluripotent cells, such as embryonic stem (ES) or induced pluripotent stem (iPS) cells. Decades of studies have led to the development of modified protocols that recapitulate molecular developmental cues by combining various growth factors and small molecules with improved efficiency. However, the later step of pancreatic differentiation into functional β-cells has yet to be satisfactory in vitro, highlighting alternative approach by recapitulating spatiotemporal multicellular interaction in three-dimensional (3D) culture. Here, we summarize recent progress in the directed differentiation into pancreatic β-cells with a focus on both two-dimensional (2D) and 3D differentiation settings. We also discuss the potential transplantation strategies in combination with current bioengineering approaches towards diabetes therapy.
Keywords: 2D, two-dimensional; 3D, three-dimensional; BMP, bone morphogenic protein; Diabetes; ES, embryonic stem; FGF, fibroblast growth factors; Heterotypic cellular interaction; IBMIR, instant blood-mediated reaction; ILV, indolactam V; Ngn3, neurogenin 3; PEG, polyethylene glycol; PI3K, phosphatidylinositol-3 kinase; PIPAAm, poly-N-isopropylacrylamide; PVA, polyvinyl alcohol; Pancreas; Pdx1, pancreatic and duodenal homeobox 1; Ptf1a, pancreatic transcription factor 1a; Regenerative medicine; VEGF, vascular endothelial growth factor; Vascularization; iPS, induced pluripotent stem; iPS/ES cell.