Intra-portal islet transplantation is the method of choice for treatment of insulin dependent type 1 diabetes, but its outcome is hindered by limited islet survival due to the immunological and metabolic stress post transplantation. Adipose-derived stromal cells (ASCs) promise to improve significantly the islet micro-environment but an efficient long-term delivery method has not been achieved. We therefore explore the potential of generating ASC enriched islet transplant structure by 3D bioprinting. Here, we fabricate a double-layered 3D bioprinted scaffold for islets and ASCs by using alginate-nanofibrillated cellulose bioink. We demonstrate the diffusion properties of the scaffold and report that human ASCs increase the islet viability, preserve the endocrine function, and reduce pro-inflammatory cytokines secretion in vitro. Intraperitoneal implantation of the ASCs and islets in 3D bioprinted scaffold improve the long-term function of islets in diabetic mice. Our data reveals an important role for ASCs on the islet micro-environment. We suggest a novel cell therapy approach of ASCs combined with islets in a 3D structure with a potential for clinical beta cell replacement therapies at extrahepatic sites.

The dataset was collected using human and mouse primary islets and human adipose-derived stromal cells (ASCs). All experiments using human materials were approved by and performed in accordance with the guidelines and regulations made by the regional committee for medical and health research ethics central in Norway. The animal experiments were approved by the Norwegian National Animal Research Authority and performed according to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health, and to the Norwegian Animal Welfare Act ( more detailed information can be found in the manuscript file).

After generating 3D bioprinted scaffolds for human or mouse islets with or withour human ASCs, in vitro and in vivo analysis were performed on the scaffolds to investigate the function of the cells after printing. For in vitro analysis, we performed glucose stimulated insulin secretion test, viability analysis and measurement of pro-inflammatory cytokines secreted by the cells in scaffolds. 

For in vivo analysis, we transplanted scaffolds at the intraperitoneal site of a diabetic mouse model to follow the function of scaffolds post transplantation.