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Betacellulin and nicotinamide sustain PDX1 expression and induce pancreatic beta-cell differentiation in human embryonic stem cells

Cited 48 time in Web of Science Cited 46 time in Scopus
Authors
Cho, Young Min; Lim, Jung Mee; Yoo, Dae Hoon; Kim, Jae Hyeon; Chung, Sung Soo; Park, Sang Gyu; Kim, Tae Hyuk; Oh, Sun Kyung; Choi, Young Min; Moon, Shin Yong; Park, Kyong Soo; Lee, Hong Kyu
Issue Date
2007
Publisher
Elsevier
Citation
Biochemical and Biophysical Research Communications 366 (2008) 129-134
Keywords
Cell Differentiation/drug effectsCell LineDose-Response Relationship, DrugEmbryonic Stem Cells/*cytology/drug effects/*physiologyGene Expression Regulation, Developmental/drug effects/physiologyHomeodomain Proteins/*metabolismHumansInsulin-Secreting Cells/*cytology/drug effects/*physiologyIntercellular Signaling Peptides and Proteins/*administration & dosageNiacinamide/*administration & dosageTrans-Activators/*metabolism
Abstract
The major obstacle in cell therapy of diabetes mellitus is the limited source of insulin-producing beta cells. Very recently, it was shown that a five-stage protocol recapitulating in vivo pancreatic organogenesis induced pancreatic beta cells in vitro; however, this protocol is specific to certain cell lines and shows much line-to-line variation in differentiation efficacy. Here, we modified the five-stage protocol for the human embryonic stem cell line SNUhES3 by the addition of betacellulin and nicotinamide. We reproduced in vivo pancreatic islet differentiation by directing the cells through stages that resembled in vivo pancreatic organogenesis. The addition of betacellulin and nicotinamide sustained PDX1 expression and induced beta-cell differentiation. C-peptide-a genuine marker of de novo insulin production-was identified in the differentiated cells, although the insulin mRNA content was very low. Further studies are necessary to develop more efficient and universal protocols for beta-cell differentiation.
ISSN
1090-2104 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18060872

http://hdl.handle.net/10371/27167
DOI
https://doi.org/10.1016/j.bbrc.2007.11.112
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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