title: Efficient generation of induced pluripotent stem cells from human bone marrow mesenchymal stem cells.
abstract: 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.
authors: Bone Marrow Transplantation Centre, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
authors: X
authors: X
authors: Yulin
authors: L
authors: L
authors: Lizhen
authors: Z
authors: Z
authors: Lifei
authors: F
authors: F
authors: Shan
authors: L
authors: L
authors: Ru
authors: H
authors: H
authors: Kaimin
authors: H
authors: H
authors: Huang
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D065150:Cellular Reprogramming / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D015415:Biomarkers; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D050814:Octamer Transcription Factor-3; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D014635:Valproic Acid; D001205:Ascorbic Acid