Tissue Engineering Strategies for Improving Beta Cell Transplantation Outcome

Abstract

Purpose of Review Beta cell replacement therapy as a form of islet transplantation is a promising alternative therapy with the possibility to make selected patients with type 1 diabetes (T1D) insulin independent. However, this technique faces challenges such as extensive activation of the host immune system post-transplantation, lifelong need for immunosuppression, and the scarcity of islet donor pancreas. Advancement in tissue engineering strategies can improve these challenges and allow for a more widespread application of this therapy. This review will discuss the recent development and clinical translation of tissue engineering strategies in beta cell replacement therapy. Recent Findings Tissue engineering offers innovative solutions for producing unlimited glucose responsive cells and fabrication of appropriate devices/scaffolds for transplantation applications. Generation of pancreatic organoids with supporting cells in biocompatible biomaterials is a powerful technique to improve the function of insulin-producing cell clusters. Fabrication of physical barriers such as encapsulation strategies can protect the cells from the host immune system and allow for graft retrieval, although this strategy still faces major challenges to fully restore physiological glucose regulation. Summary The three main components of tissue engineering strategies including the generation of stem cell-derived insulin-producing cells and organoids and the possibilities for therapeutic delivery of cell-seeded devices to extra-hepatic sites need to come together in order to provide safe and functional insulin-producing devices for clinical beta cell replacement therapy.

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

“…Explanted mIslet+hASC scaffolds were positivelylabelled for islet and ASC markers, which confirm the presence of ASCs in the scaffolds together with islets throughout the in vivo studies. Five-times Intravenous administration of 5×10 6 ASCs to diabetic mouse models has been shown less efficient since ASCs have been detected in lungs, spleen and peritubular regions but not in the pancreas post infusion [68]. However, our data shows the presence of ASCs in scaffolds 60 days post implantation and this can support the beneficial effects of ASCs on preserving the islet function.…”

“…In order to test this strategy and due to the lack of readily available human islets for this study, we fabricated 3D bioprinted scaffolds with 100 mouse islets and 1.2×10 6 human ASCs. The implantation of mIslet+hASC scaffolds to the IP site of diabetic mice could normalize blood glucose 7 days after implantation and this is almost similar to implanting full mass of mouse islets per graft (250 islets) under kidney capsule of diabetic mice.…”

“…This is mainly due to the reduced supply of oxygen and nutrients to the encapsulated islets [7][8][9][10]. One solution for more optimal islet survival is open scaffolds applying 3 dimensional (3D) bioprinting technology which allows better tissue integration and enables transplantation to more accessible extrahepatic sites such as subcutaneous and intraperitoneal [6,11,12]. Indeed, 3D bioprinting technology is being used for several cell delivery applications [13][14][15][16][17].…”

“…This leads to loss of islets, poor engraftment and decline in islet function [3–5]. Delivery of islets in hydrogel-based encapsulation scaffolds to animals and human have been explored over the years and reported to protect islets from immune rejection [6]. However, the strategy comes with a price of decreased islet survival, loss of islet function and limited clinical outcomes.…”

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

“…[5][6][7] Delivery of islets in hydrogelbased scaffolds have been explored over the years in several diabetic in vivo models and reported to have partial islet function and protection from immune rejection. [8] However, using large scaffolds comes with a price of limited oxygen, nutrients and insulin transports to and from the encapsulated islets, which subsequently lead to decreased islet survival and function. [9][10][11][12] Three-dimensional (3D) bioprinting could provide the advantages of a macroscopic delivery approach by retaining multiple islets in one potentially flat scaffold.…”