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 significant...

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Published inbioRxiv
Main Authors Abadpour, Shadab, Niemi, Essi M, Linnea Strid Orrhult, Hermanns, Carolin, De Vries, Rick, Liebert Parreiras Nogueira, Haugen, Håvard Jostein, Josefsen, Dag, Krauss, Stefan, Aart Van Apeldoorn, Gatenholm, Paul, Scholz, Hanne
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 31.05.2022
Subjects
Alginic acid
Beta cells
Cell therapy
Cellulose
Cytokines
Diabetes mellitus (insulin dependent)
Inflammation
Insulin
Islet cells
Pancreas transplantation
Pancreatic islet transplantation
Stromal cells
Transplants & implants
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Summary: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. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2022.05.30.494035