Making human pancreatic islet organoids: Progresses on the cell origins, biomaterials and three-dimensional technologies

Abstract

Diabetes is one of the most socially challenging health concerns. Even though islet transplantation has shown promise for insulin-dependent diabetes, there is still no effective method for curing diabetes due to the severe shortage of transplantable donors. In recent years, organoid technology has attracted lots of attention as organoid can mirror the human organ in vivo to the maximum extent in vitro, thus bridging the gap between cellular- and tissue/organ-level biological models. Concurrently, human pancreatic islet organoids are expected to be a considerable source of islet transplantation. To construct human islet-like organoids, the seeding cells, biomaterials and three-dimensional structure are three key elements. Herein, this review summarizes current progresses about the cell origins, biomaterials and advanced technology being applied to make human islet organoids, and discusses the advantages, shortcomings, and future challenges of them as well. We hope this review can offer a cross-disciplinary perspective to build human islet organoids and provide insights for tissue engineering and regenerative medicine.

Keywords: biomaterials; diabetes; pancreatic islet organoids; regenerative medicine; stem cells.

Figure 1

Schematic illustration of cell origin for making human islet organoids. (A-C) Many different strategies have been used to generate pancreatic endocrinal cell types, including islet lineage cells differentiated from human PSCs, islet cells and pancreatic progenitors derived from human pancreas, human β cell line and islet-like cells by trans-differentiation from non-islet lineage cells. (D) Accessory cells are proved to promote generation and vascularization of human islet organoids after long term culture or transplantation.

Figure 2

Schematic illustration of materials application of human islet organoids. (A) Usages of materials for producing human islet organoids, such as biomaterial coated, embedment and encapsulation. (B) Biomaterials can provide 3D scaffolds and mimic the native interaction with ECM for islet organoids generation, including mechanical force, topography, stiffness, signaling from ECM components and soluble factors. (C) Manufacturing process of dECM material.

Figure 3

Schematic illustration of approaches for producing human islet-like organoids. (A) Methods of constructing islet organoid 3D structure by cellular self-aggregation, including seeding cells on ultra-low-attachment plates, in spinning flasks, on biomaterial coated plates, by hanging drop and in microwell platform. (B) Mixing human islet lineage cells with hydrogel and generating 3D structure by 3D bioprinting or biomaterial embedment. (C) Methods of maintaining human islet organoids, including basketed in 3D-printed scaffold; seeded into decellularized pancreatic scaffold to form native like structure; cultured on a chip which makes it possible to model inter-organ communication in diabetes pathogenesis.