Self-assembly of three-dimensional liver organoids: virtual reconstruction via endocytosed polymer dots for refactoring the fine structure

Abstract

In vitro culture of organoids holds considerable promise for the treatment of diseases or the provision of artificial organs. Traditional 2D differentiation from mesenchymal stem cells (MSCs) faces challenges in replicating the development of embryonic organs at the cellular level; conversely, the cultivation of 3D organoids exhibits potential for application. It is crucial for clinicians and technology researchers to acquire insights into organoid tissue differentiation, autonomous morphogenesis, as well as 3D assembly processes in vitro. In this investigation, novel 3D organoids capable of engendering complex liver-like tissues in vitro were cultured, and a class of high-luminance semiconductor polymer dots (Pdots) was employed to monitor the self-assembly process of 3D liver organoid tissues and cellular interaction and migration dynamics. Three-dimensional liver-bud (3D-LB) organoid tissues were derived through the interplay of induced MSCs, Wharton's Jelly, and human umbilical vein endothelial cells (HUVECs), and their structural characteristics were determined during the liver-bud organoid development; ultimately, the co-cultured organoid spatial cellular clusters resembling a truffle were successfully replicated. Utilizing R8–Pdots with remarkable resolution and biocompatibility, the structural elements of functional and vascularized organs derived from liver organoid tissues were adeptly reconstituted, and this investigation shall contribute to a further understanding of human hepato-developmental physiology and liver-disease modeling.