Adipose-derived stromal cells preserve pancreatic islet function in a transplantable 3D bioprinted scaffold

Abstract

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.