Efficient generation of induced pluripotent stem cells from human bone marrow mesenchymal stem cells
Language English Country Czech Republic Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
23438847
PII: file/5660/FB2012A0033.pdf
Knihovny.cz E-resources
- MeSH
- Biomarkers metabolism MeSH
- Cell Culture Techniques methods MeSH
- Cell Cycle drug effects genetics MeSH
- Bone Marrow Cells cytology drug effects metabolism MeSH
- Down-Regulation genetics radiation effects MeSH
- Induced Pluripotent Stem Cells cytology drug effects metabolism MeSH
- Kruppel-Like Factor 4 MeSH
- Ascorbic Acid pharmacology MeSH
- Valproic Acid pharmacology MeSH
- Humans MeSH
- RNA, Small Interfering metabolism MeSH
- Mesenchymal Stem Cells cytology drug effects metabolism MeSH
- Multipotent Stem Cells cytology metabolism MeSH
- Mice, Inbred ICR MeSH
- Mice MeSH
- Tumor Suppressor Protein p53 metabolism MeSH
- Octamer Transcription Factor-3 genetics metabolism MeSH
- Cellular Reprogramming drug effects genetics MeSH
- Up-Regulation drug effects genetics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Biomarkers MeSH
- KLF4 protein, human MeSH Browser
- Klf4 protein, mouse MeSH Browser
- Kruppel-Like Factor 4 MeSH
- Ascorbic Acid MeSH
- Valproic Acid MeSH
- RNA, Small Interfering MeSH
- Tumor Suppressor Protein p53 MeSH
- Octamer Transcription Factor-3 MeSH
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.
