| Summary: | 博士 === 慈濟大學 === 醫學科學研究所 === 105 === Extensive human embryonic stem cells (hESCs) researches have been done in recent decades. Today, hESCs could be derived into almost all cell types of human body. However, one of the limitations of hESCs derived human cells for clinical application is the risk of teratoma formation.
In our previous study, the hESCs co-cultured with the mesenchymal stem cells derived from the Wharton’s jelly of human umbilical cord (HUCMSCs) could maintain their pluripotency but lost their ability of teratoma formation in NOD/SCID mice. However, the regulating signaling pathways were still unclear. Therefore, we intended to find a supplement which inhibits the tumorigenesis of hESCs by investigating the regulating signaling pathways in this study.
Compared to mouse embryonic fibroblasts (MEFs), HUMSCs conferred a down-regulation of WNT/β-catenin/c-myc signaling as a feeder for hESCs. Adding the β-catenin antagonist (FH535 or DKK1), could down-regulate β-catenin and c-myc expressions and suppresses tumorigenesis (3/14 vs. 4/4, p = 0.01) in hESCs fed with MEFs. whereas the a β-catenin enhancer (LiCl or 6-bromoindirubin-3′-oxime) could up-regulate the expressions and has a trend (p = 0.056) to promote tumorigenesis (2/7 vs. 0/21) in hESCs fed with HUCMSCs. Moreover, adding FH535 to the hESCs/MEFs did not affect the pluripotency of hESCs as revealed by the differentiations markers for the three germ layers.
Taken together, this study revealed WNT/β-catenin/c-myc is an important signaling pathway conferring tumorigenicity of hESCs and explain the non-tumorigenic feature of HUCMSC co-culture. β-catenin inhibitor could be used to improve the tumorigenicity while not compromising the pluripotency of hESCs.
Keywords: human embryonic stem cells, human umbilical cord mesenchymal stem cells, mouse embryonic fibroblasts, teratoma, tumorigenesis, differentiation
|
|---|
