Betacellulin and nicotinamide sustain PDX1 expression and induce pancreatic beta-cell differentiation in human embryonic stem cells.
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.
Cho
Young Min
YM
Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-744, Republic of Korea.
Lim
Jung Mee
JM
Yoo
Dae Hoon
DH
Kim
Jae Hyeon
JH
Chung
Sung Soo
SS
Park
Sang Gyu
SG
Kim
Tae Hyuk
TH
Oh
Sun Kyung
SK
Choi
Young Min
YM
Moon
Shin Yong
SY
Park
Kyong Soo
KS
Lee
Hong Kyu
HK
D066259:Betacellulin; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D009536:Niacinamide / Q000008:administration & dosage*; D015534:Trans-Activators / Q000378:metabolism*
C587851:BTC protein, human; D066259:Betacellulin; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D009536:Niacinamide