Journal ArticleDOI
Cell-surface markers for the isolation of pancreatic cell types derived from human embryonic stem cells
Olivia Kelly,Man Yin Chan,Laura Martinson,Kuniko Kadoya,Traci M Ostertag,Kelly G. Ross,Mike Richardson,Melissa K. Carpenter,Kevin A. D'Amour,Evert Kroon,Mark A. Moorman,Emmanuel E. Baetge,Anne G. Bang +12 more
TLDR
Using a flow cytometry–based screen of commercial antibodies, cell-surface markers for the separation of pancreatic cell types derived from human embryonic stem (hES) cells are identified and will aid investigations that use pancreatic cells generated from pluripotent stem cells to study diabetes and pancreas biology.Abstract:
Using a flow cytometry-based screen of commercial antibodies, we have identified cell-surface markers for the separation of pancreatic cell types derived from human embryonic stem (hES) cells. We show enrichment of pancreatic endoderm cells using CD142 and of endocrine cells using CD200 and CD318. After transplantation into mice, enriched pancreatic endoderm cells give rise to all the pancreatic lineages, including functional insulin-producing cells, demonstrating that they are pancreatic progenitors. In contrast, implanted, enriched polyhormonal endocrine cells principally give rise to glucagon cells. These antibodies will aid investigations that use pancreatic cells generated from pluripotent stem cells to study diabetes and pancreas biology.read more
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Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells
Alireza Rezania,Jennifer E. Bruin,Payal Arora,Allison Rubin,Irina Batushansky,Ali Asadi,Shannon O'Dwyer,Nina Quiskamp,Majid Mojibian,Tobias Albrecht,Yu Hsuan Carol Yang,James D. Johnson,Timothy J. Kieffer +12 more
TL;DR: Although S7 cells are not fully equivalent to mature beta cells, their capacity for glucose-responsive insulin secretion and rapid reversal of diabetes in vivo makes them a promising alternative to pancreatic progenitor cells or cadaveric islets for the treatment of diabetes.
Journal ArticleDOI
Maturation of Human Embryonic Stem Cell–Derived Pancreatic Progenitors into Functional Islets Capable of Treating Pre-existing Diabetes in Mice
Alireza Rezania,Jennifer E. Bruin,Michael J. Riedel,Majid Mojibian,Ali Asadi,Jean Xu,Rebecca Gauvin,Kavitha Narayan,Francis Karanu,John J. O'Neil,Ziliang Ao,Garth L. Warnock,Timothy J. Kieffer +12 more
TL;DR: A protocol to efficiently differentiate commercially available human embryonic stem cells in vitro into a highly enriched PDX1+ pancreatic progenitor cell population that further develops in vivo to mature pancreatic endocrine cells supports the feasibility of using differentiated hESCs as an alternative to cadaveric islets for treating patients with diabetes.
Journal ArticleDOI
A Scalable System for Production of Functional Pancreatic Progenitors from Human Embryonic Stem Cells
Thomas C. Schulz,Holly Y. Young,Alan D. Agulnick,M. Josephine Babin,Emmanuel E. Baetge,Anne G. Bang,Anindita Bhoumik,Igor Cepa,Rosemary M. Cesario,Carl Haakmeester,Kuniko Kadoya,Jonathan R. Kelly,Justin Kerr,Laura Martinson,Amanda B. McLean,Mark A. Moorman,Janice K. Payne,Mike Richardson,Kelly G. Ross,Eric S. Sherrer,Xuehong Song,Alistair Wilson,Eugene P. Brandon,Chad Green,Evert Kroon,Olivia Kelly,Kevin A. D'Amour,Allan J. Robins +27 more
TL;DR: A tractable manufacturing process for the generation of functional pancreatic progenitors from hESC on a scale amenable to clinical entry is developed.
Journal ArticleDOI
Pluripotent stem cells in regenerative medicine: challenges and recent progress
Viviane Tabar,Lorenz Studer +1 more
TL;DR: Recent progress in directed differentiation, some of the new technologies that have facilitated the success of hPSC therapies and the remaining hurdles on the road towards developing hPSc-based cell therapies are discussed.
PatentDOI
Controlled Induction of Human Pancreatic Progenitors Produces Functional Beta-Like Cells
Matthias Hebrok,Holger A. Russ +1 more
TL;DR: In this article, a simple, fast, effective and safe directed differentiation of embryonic stem cells into pancreatic beta-like cells secreting insulin in response to glucose levels is described.
References
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Journal ArticleDOI
Production of pancreatic hormone–expressing endocrine cells from human embryonic stem cells
Kevin A. D'Amour,Anne G. Bang,Susan Eliazer,Olivia Kelly,Alan D. Agulnick,Nora G Smart,Mark A. Moorman,Evert Kroon,Melissa K Carpenter,Emmanuel E. Baetge +9 more
TL;DR: A differentiation process that converts human embryonic stem cells to endocrine cells capable of synthesizing the pancreatic hormones insulin, glucagon, somatostatin, pancreatic polypeptide and ghrelin is developed.
Journal ArticleDOI
Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo
Evert Kroon,Laura Martinson,Kuniko Kadoya,Anne G. Bang,Olivia Kelly,Susan Eliazer,Holly Y. Young,Mike Richardson,Nora G. Smart,Justine J Cunningham,Alan D. Agulnick,Kevin A. D'Amour,Melissa K. Carpenter,Emmanuel E. Baetge +13 more
TL;DR: It is shown that pancreatic endoderm derived from human embryonic stem (hES) cells efficiently generates glucose-responsive endocrine cells after implantation into mice, and it is demonstrated that implantation of hES cell–derived pancreaticEndoderm protects against streptozotocin-induced hyperglycemia.
Journal ArticleDOI
Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors.
TL;DR: The results provide direct evidence that NGN3+ cells are islet progenitors during embryogenesis and in adult mice, and suggest that lineages for exocrine, endocrine islet and duct progenitor are committed at mid-gestation.