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Differentiation of human embryonic stem cells into pancreatic endoderm in patterned size-controlled clusters.
- Source :
-
Stem cell research [Stem Cell Res] 2011 May; Vol. 6 (3), pp. 276-85. Date of Electronic Publication: 2011 Mar 02. - Publication Year :
- 2011
-
Abstract
- Pancreatic β-cells function optimally when clustered in islet-like structures. However, nutrient and oxygen deprivation limits the viability of cells at the core of excessively large clusters. Hence, production of functional β-cells from human embryonic stem cells (hESCs) for patients with diabetes would benefit from the growth and differentiation of these cells in size-controlled aggregates. In this study, we controlled cluster size by seeding hESCs onto glass cover slips patterned by the covalent microcontact-printing of laminin in circular patches of 120 μm in diameter. These were used as substrates to grow and differentiate hESCs first into SOX17-positive/SOX7-negative definitive endoderm, after which many clusters released and formed uniformly sized three-dimensional clusters. Both released clusters and those that remained attached differentiated into HNF1β-positive primitive gut tube-like cells with high efficiency. Further differentiation yielded pancreatic endoderm-like cells that co-expressed PDX1 and NKX6.1. Controlling aggregate size allows efficient production of uniformly-clustered pancreatic endocrine precursors for in vivo engraftment or further in vitro maturation.<br /> (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Subjects :
- Cell Size
Embryonic Stem Cells metabolism
Endoderm metabolism
Gene Expression
Homeodomain Proteins genetics
Homeodomain Proteins metabolism
Humans
Insulin-Secreting Cells cytology
Insulin-Secreting Cells metabolism
Pancreas growth & development
Pancreas metabolism
Trans-Activators genetics
Trans-Activators metabolism
Cell Culture Techniques methods
Cell Differentiation
Embryonic Stem Cells cytology
Endoderm cytology
Pancreas cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1876-7753
- Volume :
- 6
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Stem cell research
- Publication Type :
- Academic Journal
- Accession number :
- 21513906
- Full Text :
- https://doi.org/10.1016/j.scr.2011.02.004