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Generation of functional human pancreatic organoids by transplants of embryonic stem cell derivatives in a 3D‐printed tissue trapper
Author(s) -
Soltanian Anahita,
Ghezelayagh Zahra,
Mazidi Zahra,
Halvaei Majid,
Mardpour Soura,
Ashtiani Mohammad Kazemi,
HajizadehSaffar Ensiyeh,
Tahamtani Yaser,
Baharvand Hossein
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27644
Subject(s) - organoid , embryonic stem cell , pdx1 , stem cell , regenerative medicine , progenitor cell , mesenchymal stem cell , microbiology and biotechnology , matrigel , induced pluripotent stem cell , tissue engineering , biology , transplantation , cell , anatomy , medicine , islet , endocrinology , diabetes mellitus , biochemistry , genetics , gene
Abstract Organoids can be regarded as a beneficial tool for discovery of new therapeutics for diabetes and/or maturation of pancreatic progenitors (PP) towards β cells. Here, we devised a strategy to enhance maturation of PP by assembly of three‐dimensional (3D) pancreatic organoids (PO) containing human embryonic stem (ES) cell derivatives including ES‐derived pancreatic duodenal homeobox 1 (PDX1) + early PP, mesenchymal stem cells, and endothelial cells at an optimized cell ratio, on Matrigel. The PO was placed in a 3D‐printed tissue trapper and heterotopically implanted into the peritoneal cavity of immunodeficient mice where it remained for 90 days. Our results indicated that, in contrast to corresponding early PP transplants, 3D PO developed more vascularization as indicated by greater area and number of vessels, a higher number of insulin‐positive cells and improvement of human C‐peptide secretions. Based on our findings, PO‐derived β cells could be considered a novel strategy to study human β‐cell development, novel therapeutics, and regenerative medicine for diabetes.