title: Development of Islet Organoids from H9 Human Embryonic Stem Cells in Biomimetic 3D Scaffolds.
abstract: Success in the differentiating human embryonic stem cells (hESCs) into insulin-secreting β cells raises new hopes for diabetes treatment. In this work, we demonstrated the feasibility of developing islet organoids from hESCs within biomimetic 3D scaffolds. We showed that such a 3D microenvironment is critical to the generation of pancreatic endoderm and endocrine from hESCs. The organoids formed consisted of pancreatic α, β, δ, and pancreatic polypeptide (PP) cells. A high-level co-expression of PDX1, NKX6.1, and NGN3 in these cells suggests the characteristics of pancreatic β cells. More importantly, most insulin-secreting cells generated did not express glucagon, somatostatin, or PP. The expression of mature β cell marker genes such as Pdx1, Ngn3, Insulin, MafA, and Glut2 was detected in these 3D-induced cell clusters. A high-level expression of C-peptide confirmed the de novo endogenous insulin production in these 3D induced cells. Insulin-secretory granules, an indication of β cell maturity, were detected in these cells as well. Glucose challenging experiments suggested that these cells are sensitive to glucose levels due to their elevated maturity. Exposing the cells to a high concentration of glucose induced a sharp increase in insulin secretion.
authors.affiliation: 1 Department of Biomedical Engineering, College of Engineering, University of Arkansas , Fayetteville, Arkansas.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.affiliation: 1 Department of Biomedical Engineering, College of Engineering, University of Arkansas , Fayetteville, Arkansas.|2 Department of Biomedical Engineering, Center of Biomanufacturing for Regenerative Medicine, Watson School of Engineering and Applied Science, Binghamton University, State University of New York (SUNY) , Binghamton, New York.
authors.forename: Sha
authors.initials: S
authors.lastname: Jin
authors.affiliation: 1 Department of Biomedical Engineering, College of Engineering, University of Arkansas , Fayetteville, Arkansas.|2 Department of Biomedical Engineering, Center of Biomanufacturing for Regenerative Medicine, Watson School of Engineering and Applied Science, Binghamton University, State University of New York (SUNY) , Binghamton, New York.
authors.forename: Kaiming
authors.initials: K
authors.lastname: Ye
mesh_terms: D000328:Adult; D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D004707:Endoderm / Q000166:cytology / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000494:pharmacology; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007769:Lactams / Q000494:pharmacology; D007797:Laminin / Q000494:pharmacology; D009940:Organoids / Q000166:cytology*; D011509:Proteoglycans / Q000494:pharmacology; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D004338:Drug Combinations; D007328:Insulin; D007769:Lactams; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D005947:Glucose
keywords: 3D stem cell differentiation; diabetes; human embryonic stem cell differentiation; insulin-producing beta-cells; islet organoids; islets development; organoid development