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Open Access 01-11-2016 | Article

Effective endothelial cell and human pluripotent stem cell interactions generate functional insulin-producing beta cells

Authors: Dodanim Talavera-Adame, Orison O. Woolcott, Joseph Ignatius-Irudayam, Vaithilingaraja Arumugaswami, David H. Geller, Donald C. Dafoe

Published in: Diabetologia | Issue 11/2016

Abstract

Aims/hypothesis

Endothelial cells (ECs) play an essential role in pancreatic organogenesis. We hypothesise that effective in vitro interactions between human microvascular endothelial cells (HMECs) and human pluripotent stem cells (hPSCs) results in the generation of functional pancreatic beta cells.

Methods

Embryoid bodies (EBs) derived from hPSCs were cultured alone (controls) or with ECs in collagen gels. Subsequently, cells were analysed for pancreatic beta cell markers, and then isolated and expanded. Insulin secretion in response to glucose was evaluated in vitro by static and dynamic (perifusion) assays, and in vivo by EB transplantation into immunodeficient mice.

Results

Co-cultured EBs had a higher expression of mature beta cells markers and enhanced insulin secretion in vitro, compared with controls. In mice, transplanted EBs had higher levels of human C-peptide secretion with a significant reduction in hyperglycaemia after the selective destruction of native pancreatic beta cells. In addition, there was significant in vitro upregulation of bone morphogenetic proteins 2 and 4 (BMP-2, 4) in co-cultured cells, compared with controls.

Conclusions/interpretation

ECs provide essential signalling in vitro, such as activation of the BMP pathway, for derivation of functional insulin-producing beta cells from hPSCs.

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Title: Effective endothelial cell and human pluripotent stem cell interactions generate functional insulin-producing beta cells
Authors: Dodanim Talavera-Adame
Orison O. Woolcott
Joseph Ignatius-Irudayam
Vaithilingaraja Arumugaswami
David H. Geller
Donald C. Dafoe
Publication date: 01-11-2016
Publisher: Springer Berlin Heidelberg
Published in: Diabetologia / Issue 11/2016
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-016-4078-1

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