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

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.