Adipose-Derived Stromal Cells Preserve Pancreatic Islet Function in a Transplantable 3D Bioprinted Scaffold
Journal article, 2023
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.
ASC
3D bioprinting
in vivo
islets
scaffolds
nanocellulose
alginate
Author
Shadab Abadpour
University of Oslo
Oslo University Hospital
Institute for Surgical Research
Essi M. Niemi
University of Oslo
Institute for Surgical Research
Aker University Hospital
Linnea Strid Orrhult
Chalmers, Chemistry and Chemical Engineering, Applied Chemistry
Carolin Hermanns
Maastricht University
Rick de Vries
Maastricht University
Liebert Parreiras Nogueira
University of Oslo
Havard J. Haugen
University of Oslo
Dag Josefsen
Rikshospitalet-Radiumhospitalet HF
Stefan Krauss
Oslo University Hospital
University of Oslo
Paul Gatenholm
Chalmers, Chemistry and Chemical Engineering, Applied Chemistry
Cellheal AS
Aart van Apeldoorn
Maastricht University
Hanne Scholz
Institute for Surgical Research
Rikshospitalet-Radiumhospitalet HF
University of Oslo
Oslo University Hospital
Advanced healthcare materials
2192-2640 (ISSN) 2192-2659 (eISSN)
Vol. 12 32 2300640Subject Categories
Surgery
Cell and Molecular Biology
Gastroenterology and Hepatology
DOI
10.1002/adhm.202300640
PubMed
37781993