Functional Beta Cell Mass from Device-Encapsulated hESC-Derived Pancreatic Endoderm Achieving Metabolic Control
Human stem cells represent a potential source for implants that replace the depleted functional beta cell mass (FBM) in diabetes patients. Human embryonic stem cell-derived pancreatic endoderm (hES-PE) can generate implants with glucose-responsive beta cells capable of reducing hyperglycemia in mice...
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Published in | Stem cell reports Vol. 10; no. 3; pp. 739 - 750 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
13.03.2018
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | Human stem cells represent a potential source for implants that replace the depleted functional beta cell mass (FBM) in diabetes patients. Human embryonic stem cell-derived pancreatic endoderm (hES-PE) can generate implants with glucose-responsive beta cells capable of reducing hyperglycemia in mice. This study with device-encapsulated hES-PE (4 × 106 cells/mouse) determines the biologic characteristics at which implants establish metabolic control during a 50-week follow-up. A metabolically adequate FBM was achieved by (1) formation of a sufficient beta cell number (>0.3 × 106/mouse) at >50% endocrine purity and (2) their maturation to a functional state comparable with human pancreatic beta cells, as judged by their secretory responses during perifusion, their content in typical secretory vesicles, and their nuclear NKX6.1-PDX1-MAFA co-expression. Assessment of FBM in implants and its correlation with in vivo metabolic markers will guide clinical translation of stem cell-derived grafts in diabetes.
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•Human stem cell-derived pancreatic precursors generate functional beta cell mass•Cellular markers identify metabolically adequate human stem cell-generated implants•Significance of determining beta cell number and maturation in implants•Functional implants differ in endocrine composition from endocrine pancreas
In this article, Pipeleers and colleagues demonstrate that subcutaneous implants of device-encapsulated human stem cell-derived pancreatic endoderm can generate a functional beta cell mass that establishes sustained glucose control in mice. They identified their biologic characteristics and correlation with in vivo outcome. Data and methods are expected to guide clinical translation to beta cell replacement therapy in diabetes. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2213-6711 2213-6711 |
DOI: | 10.1016/j.stemcr.2018.01.040 |