Adipose‐Derived Stromal Cells Preserve Pancreatic Islet Function in a Transplantable 3D Bioprinted Scaffold

Abstract

Intra‐portal islet transplantation is currently the only clinically approved beta cell replacement therapy, but its outcome is hindered by limited cell survival due to a multifactorial reaction against the allogeneic tissue in liver. Adipose‐derived stromal cells (ASCs) can potentially improve the islet micro‐environment by their immunomodulatory action. The challenge is to combine both islets and ASCs in a relatively easy and consistent long‐term manner in a deliverable scaffold. Manufacturing the 3D bioprinted double‐layered scaffolds with primary islets and ASCs using a mix of alginate/nanofibrillated cellulose (NFC) bioink is reported. The diffusion properties of the bioink and the supportive effect of human ASCs on islet viability, glucose sensing, insulin secretion, and reducing the secretion of pro‐inflammatory cytokines are demonstrated. Diabetic mice transplanted with islet‐ASC scaffolds reach normoglycemia seven days post‐transplantation with no significant difference between this group and the group received islets under the kidney capsules. In addition, animals transplanted with islet‐ASC scaffolds stay normoglycemic and show elevated levels of C‐peptide compared to mice transplanted with islet‐only scaffolds. The data present a functional 3D bioprinted scaffold for islets and ASCs transplanted to the extrahepatic site and suggest a possible role of ASCs on improving the islet micro‐environment.

Recent Advances in Alginate-Based Hydrogels for Cell Transplantation Applications

“…Another approach to prevent collapsing during printing involves the incorporation of nanofibers into the bioink formulated with alginate. One such example features the use of nanofibrillated cellulose within an alginate solution to create 3D bioprinted scaffolds known for their shape stability [ 126 , 127 ]. An additional example involves the incorporation of polylactic acid (PLA) nanofibers into a bioink formulation consisting of an alginate hydrogel and human adipose-derived stem cells (hASC) [ 128 ].…”

“…Recently, Abadpour et al presented novel findings on the supportive role of adipose-derived stem cells (ASCs) in pancreatic islets within 3D bioprinted scaffolds comprised of alginate and nanofibrillated cellulose [ 126 ] ( Figure 4 h). Their scaffold design features a distinctive double-layered structure, hosting mouse or human pancreatic islets in the top grid layer and human ASCs in the lower layer.…”

“…One pump is loaded with the pre-hydrogel, while the other contains CaCl 2 as crosslinking solution ( g ), adapted with permission from [ 136 ]. ( Lower right panel ): The 3D bioprinted scaffold featuring two layers: pancreatic islets in the upper layer and ASCs in the lower layer ( h ), adapted with permission from [ 126 ].…”