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Stem Cells Dev. 2017 Mar 15;26(6):394-404. doi: 10.1089/scd.2016.0115. Epub 2017 Jan 11.

Development of Islet Organoids from H9 Human Embryonic Stem Cells in Biomimetic 3D Scaffolds.

Wang W1, Jin S1,2, Ye K1,2.

Author information

1
1 Department of Biomedical Engineering, College of Engineering, University of Arkansas , Fayetteville, Arkansas.
2
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.

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.

KEYWORDS:

3D stem cell differentiation; diabetes; human embryonic stem cell differentiation; insulin-producing beta-cells; islet organoids; islets development; organoid development

PMID:
27960594
DOI:
10.1089/scd.2016.0115
[Indexed for MEDLINE]

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