Functional Beta Cell Mass from Device-Encapsulated HESC-Derived Pancreatic Endoderm Achieving Metabolic Control

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2018 Mar 6

PMID 29503087

Citations 28

Authors

Thomas Robert

Ines De Mesmaeker

Geert M Stange

Krista G Suenens

Zhidong Ling

Evert J Kroon

Daniel G Pipeleers

Affiliations

Soon will be listed here.

Abstract

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 × 10 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 × 10/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.

Citing Articles

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