Bioprinting vascularized human islet tissue models via aggregate-based co-culture and self-assembly

Abstract

Diabetes is a significant global metabolic disease. Current treatments, including islet or pancreas transplantation and insulin therapy, are limited by donor shortages and suboptimal glycemic control. Islet organoids, three-dimensional (3D) cell aggregates that mimic pancreatic islets, offer a powerful tool for diabetes research, drug screening, and transplantation therapies. However, challenges remain in engineering methods for the scalable preparation of human islet organoids (hIOs) with homogeneous consistency and controllable incorporation of vascular elements. In this study, we developed a novel bioengineering approach for the stable production of human islet tissue models with vascular elements using a combination of 3D bioprinting-based organoid co-culture and cell self-assembly principles. Human adipose-derived mesenchymal stem cells were differentiated into massive and uniform human islet β-like cell aggregates (hICAs) using an off-the-shelf polydimethylsiloxane user-defined micropatterning platform system. A tri-module thermal-controlled bioprinting process employing a gelatin–alginate– Matrigel bioink was used for the 3D bioprinting of hICAs and human umbilical vein endothelial cells (HUVECs). Compared with bioprinted hICAs alone, co-bioprinted and co-cultured hICAs and HUVECs more effectively recapitulated the morphogenesis of human islet development, significantly upregulated the expression of pancreatic islet- and endothelial cell-related markers, and enhanced islet function, namely glucose-stimulated insulin secretion. Thus, the self-assembly of hICAs and HUVECs to form hIOs with vascular elements mimics natural human pancreatic islets and may promote functional maturity. Our method provides a scalable platform for generating vascularized aggregation-based tissue models, supporting studies of pancreatic development and diabetes therapy.  

Keywords

Bioprinting / Human adipose-derived mesenchymal stem cells / Human islet tissue models / Islet β-like cell aggregates

Funding

This study was supported by the National Key Research and Development Program of China (2022YFA1104600; 2018YFA0109000).

Conflict of Interest

The authors declare that they have no conflict of interest.

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