Pancreatic tissue formation from murine embryonic stem cells in vitro.
The in vitro formation of organs and/or tissues is a major goal for regenerative medicine that would also provide a powerful tool for analyzing both the mechanisms of development and disease processes for each target organ. Here, we present a method whereby pancreatic tissues can be formed in vitro from mouse embryonic stem (ES) cells. Embryoid body-like spheres (EBSs) induced from ES cell colonies were treated with retinoic acid (RA) and activin, which are candidate regulators of pancreatic development in vivo. These induced tissues had decreased expression of the sonic hedgehog (shh) gene and expressed several pancreatic marker genes. ES cell-derived pancreatic tissue was composed of exocrine cells, endocrine cells, and pancreatic duct-like structures. In addition, the ratio of exocrine to endocrine cells in the induced tissue was found to be sensitive to the concentrations of RA and activin in the present experiment.
Nakanishi
Mio
M
Department of Life Science (Biology), Graduate School of Arts & Science, University of Tokyo, Meguro, Tokyo 153-8902, Japan. asashi@bio.c.u-tokyo.ac.jp
Hamazaki
Tatsuo S
TS
Komazaki
Shinji
S
Okochi
Hitoshi
H
Asashima
Makoto
M
D028341:Activins / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics; D053595:Embryonic Stem Cells / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D005934:Glucagon / Q000235:genetics; D053823:Hedgehog Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D007328:Insulin / Q000235:genetics; D051379:Mice; D010179:Pancreas / Q000737:chemistry / Q000166:cytology / Q000254:growth & development*; D010191:Pancreatic Polypeptide / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D046509:Tissue Culture Techniques; D015534:Trans-Activators / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology; D000516:alpha-Amylases / Q000235:genetics
D015415:Biomarkers; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D007328:Insulin; D012333:RNA, Messenger; C465570:Shh protein, mouse; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D028341:Activins; D014212:Tretinoin; D010191:Pancreatic Polypeptide; D005934:Glucagon; D000516:alpha-Amylases