Generation of functional human pancreatic organoids by transplants of embryonic stem cell derivatives in a 3D‐printed tissue trapper. Issue 6 (26th October 2018)

• Record Type: Journal Article
• Authors: Soltanian, Anahita; Ghezelayagh, Zahra; Mazidi, Zahra; Halvaei, Majid; Mardpour, Soura; Ashtiani, Mohammad Kazemi; Hajizadeh‐Saffar, Ensiyeh; Tahamtani, Yaser; Baharvand, Hossein
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 6(2019:Jun.)
• Page Start: 9564
• Page End: 9576
• Publication Date: 2018-10-26
• Subjects: 3D‐printed device -- organoid -- pancreatic progenitor cells -- self‐organization; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.27644
• Languages: English
• ISSNs: 0021-9541

Abstract

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. 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. 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 indicate that 3D PO developed more vascularization, a higher number of insulin‐positive cells and improvement of human C‐peptide secretions. ES‐PP: ES cell‐derived pancreatic progenitors; ES‐MSC: ES cell‐derived mesenchymal stem cells; ES‐EC: ES cell‐derived endothelial cells; GF: growth factor; GFR: growth factor reduced; SM: small molecule; IP Tx: intraperitoneal transplantation