Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets.
Although the source of embryonic stem (ES) cells presents ethical concerns, their use may lead to many clinical benefits if differentiated cell types can be derived from them and used to assemble functional organs. In pancreas, insulin is produced and secreted by specialized structures, islets of Langerhans. Diabetes, which affects 16 million people in the United States, results from abnormal function of pancreatic islets. We have generated cells expressing insulin and other pancreatic endocrine hormones from mouse ES cells. The cells self-assemble to form three-dimensional clusters similar in topology to normal pancreatic islets where pancreatic cell types are in close association with neurons. Glucose triggers insulin release from these cell clusters by mechanisms similar to those employed in vivo. When injected into diabetic mice, the insulin-producing cells undergo rapid vascularization and maintain a clustered, islet-like organization.
Lumelsky
N
N
Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4092, USA.
Blondel
O
O
Laeng
P
P
Velasco
I
I
Ravin
R
R
McKay
R
R
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002118:Calcium / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002449:Cell Aggregation; D002454:Cell Differentiation; D002455:Cell Division; D000242:Cyclic AMP / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000098:blood supply / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D015415:Biomarkers; D007328:Insulin; D012333:RNA, Messenger; D000242:Cyclic AMP; D005947:Glucose; D011188:Potassium; D002118:Calcium