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.

An FDA-Validated, Self-Cleaning Liquid Chromatography–Mass Spectrometry System for Determining Small-Molecule Drugs and Metabolites in Organoid/Organ-on-Chip Medium

“…Liver organoids were generated from human-induced pluripotent stem cells (H1 ESC cell line, WiCell, HMGUi001-A, HMGU, and WTC-11, Coriell Institute for Medical Research) as previously described. 14,17 After the differentiation protocol, liver organoids were cultured in static conditions in 24 well plates and on the pump-less recirculating OoC (rOoC 15 ) platform. Organoids, both in static cultivation and an rOoC, were exposed to tolbutamide-supplemented medium (25−40 μM concentrations) for 24 h.…”

Long-term cultures of human pancreatic islets in self-assembling peptides hydrogels

“…Human pancreatic organoids could have opportunity to produce functional β-cells in vitro after human pluripotent stem cells differentiation process and could acts as source of islets for transplantation (Jiang et al, 2022;Yin et al, 2022). A tissue engineering approach is required for culturing insulin-producing cells in a ECM-like scaffold in threedimensional (3D) constructs with the purpose to restore cellmatrix attachment and to maintain islet viability and insulin secretion functionality for long-time (Kumar et al, 2018;Elizondo et al, 2020;Abadpour et al, 2022;Perugini et al, 2022). Islet encapsulation within bioscaffold may provide an immune-isolation strategy for islet transplantation and engraftment, avoiding immune-suppression procedure to prevent rejection.…”