Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo.
Development of a cell therapy for diabetes would be greatly aided by a renewable supply of human beta-cells. Here we show that pancreatic endoderm derived from human embryonic stem (hES) cells efficiently generates glucose-responsive endocrine cells after implantation into mice. Upon glucose stimulation of the implanted mice, human insulin and C-peptide are detected in sera at levels similar to those of mice transplanted with approximately 3,000 human islets. Moreover, the insulin-expressing cells generated after engraftment exhibit many properties of functional beta-cells, including expression of critical beta-cell transcription factors, appropriate processing of proinsulin and the presence of mature endocrine secretory granules. Finally, in a test of therapeutic potential, we demonstrate that implantation of hES cell-derived pancreatic endoderm protects against streptozotocin-induced hyperglycemia. Together, these data provide definitive evidence that hES cells are competent to generate glucose-responsive, insulin-secreting cells.
Kroon
Evert
E
Novocell, Inc., 3550 General Atomics Ct., San Diego, California 92121, USA.
Martinson
Laura A
LA
Kadoya
Kuniko
K
Bang
Anne G
AG
Kelly
Olivia G
OG
Eliazer
Susan
S
Young
Holly
H
Richardson
Mike
M
Smart
Nora G
NG
Cunningham
Justine
J
Agulnick
Alan D
AD
D'Amour
Kevin A
KA
Carpenter
Melissa K
MK
Baetge
Emmanuel E
EE
D000818:Animals; D018929:Cell Culture Techniques / Q000639:trends*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism* / Q000637:transplantation; D051379:Mice; D019397:Pancreas, Artificial / Q000639:trends; D023822:Tissue Engineering / Q000639:trends*
D007328:Insulin; D005947:Glucose