Ectopic expression of defined sets of genetic factors can reprogramme somatic cells to induced pluripotent stem cells (iPSCs) that closely resemble embryonic stem cells. However, the low reprogramming efficiency is a significant handicap for mechanistic studies and potential clinical application. In this study, we used human bone marrow-derived mesenchymal stem cells (hBMMSCs) as target cells for reprogramming and investigated efficient iPSC generation from hBMMSCs using the compounds of p53 siRNA, valproic acid (VPA) and vitamin C (Vc) with four transcription factors OCT4, SOX2, KLF4, and c-MYC (compound induction system). The synergetic mechanism of the compounds was studied. Our results showed that the compound induction system could efficiently reprogramme hBMMSCs to iPSCs. hBMMSC-derived iPSC populations expressed pluripotent markers and had multi-potential to differentiate into three germ layer-derived cells. p53 siRNA, VPA and Vc had a synergetic effect on cell reprogramming and the combinatorial use of these substances greatly improved the efficiency of iPSC generation by suppressing the expression of p53, decreasing cell apoptosis, up-regulating the expression of the pluripotent gene OCT4 and modifying the cell cycle. Therefore, our study highlights a straightforward method for improving the speed and efficiency of iPSC generation and provides versatile tools for investigating early developmental processes such as haemopoiesis and relevant diseases. In addition, this study provides a paradigm for the combinatorial use of genetic factors and molecules to improve the efficiency of iPSC generation.
- MeSH
- biologické markery metabolismus MeSH
- buněčné kultury metody MeSH
- buněčný cyklus účinky léků genetika MeSH
- buňky kostní dřeně cytologie účinky léků metabolismus MeSH
- down regulace genetika účinky záření MeSH
- indukované pluripotentní kmenové buňky cytologie účinky léků metabolismus MeSH
- kyselina askorbová farmakologie MeSH
- kyselina valproová farmakologie MeSH
- lidé MeSH
- malá interferující RNA metabolismus MeSH
- mezenchymální kmenové buňky cytologie účinky léků metabolismus MeSH
- multipotentní kmenové buňky cytologie metabolismus MeSH
- myši inbrední ICR MeSH
- myši MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- oktamerní transkripční faktor 3 genetika metabolismus MeSH
- přeprogramování buněk účinky léků genetika MeSH
- upregulace účinky léků genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
