Oxygenated Scaffolds for Pancreatic Endocrine Differentiation from Induced Pluripotent Stem Cells

Abstract

A three‐dimensional (3D) microenvironment is known to endorse pancreatic islet development from human induced pluripotent stem cells (iPSCs). However, oxygen supply becomes a limiting factor in a scaffold culture. In this study, we fabricated oxygen release biomaterials and developed an oxygenated scaffold culture platform to offer a better oxygen supply during 3D iPSC pancreatic differentiation. We found that the oxygenation does not alter the scaffold's mechanical properties. The in‐situ oxygenation improves oxygen tension within the scaffolds. The unique 3D differentiation system enabled the generation of islet organoids with enhanced expression of islet signature genes and proteins. Additionally, we discovered that the oxygenation at the early stage of differentiation has more profound impacts on islet development from iPSCs. More C‐peptide+/MAFA+ β and glucagon+/MAFB+ α cells formed in the iPSC‐derived islet organoids generated under oxygenation conditions, suggesting enhanced maturation of the organoids. Furthermore, the oxygenated 3D cultures improved islet organoids’ sensitivity to glucose for insulin secretion. We herein demonstrated that the oxygenated scaffold culture empowers iPSC islet differentiation to generate clinically relevant tissues for diabetes research and treatment.This article is protected by copyright. All rights reserved

Traditional and emerging strategies using hepatocytes for pancreatic regenerative medicine

“…R‐Spondin1 is an agonist of the LGR5 receptor of the Wnt/β‐catenin pathway, which in turn is essential for the development and self‐renewal of several types of adult stem cells 86 . At the same time, FGF10, nicotinamide, N‐acetylcysteine, and B27 are also widely used as components of pancreatic islet organoid media 87 . FGF10 promotes PDX1 + pancreatic progenitor cell expansion and aids pancreatic progenitor cell growth and differentiation 88,89 .…”

“… 86 At the same time, FGF10, nicotinamide, N‐acetylcysteine, and B27 are also widely used as components of pancreatic islet organoid media. 87 FGF10 promotes PDX1 + pancreatic progenitor cell expansion and aids pancreatic progenitor cell growth and differentiation. 88 , 89 Nicotinamide induces fetal pancreatic endocrine cell differentiation and maturation and is commonly used for islet organoid culture.…”