Efficient Commitment to Functional CD34 Progenitor Cells from Human Bone Marrow Mesenchymal Stem-Cell-Derived Induced Pluripotent Stem CellsReportar como inadecuado




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The efficient commitment of a specialized cell type from induced pluripotent stem cells iPSCs without contamination from unknown substances is crucial to their use in clinical applications. Here, we propose that CD34+ progenitor cells, which retain hematopoietic and endothelial cell potential, could be efficiently obtained from iPSCs derived from human bone marrow mesenchymal stem cells hBMMSC-iPSCs with defined factors. By treatment with a cocktail containing mesodermal, hematopoietic, and endothelial inducers BMP4, SCF, and VEGF, respectively for 5 days, hBMMSC-iPSCs expressed the mesodermal transcription factors Brachyury and GATA-2 at higher levels than untreated groups P<0.05. After culturing with another hematopoietic and endothelial inducer cocktail, including SCF, Flt3L, VEGF and IL-3, for an additional 7–9 days, CD34+ progenitor cells, which were undetectable in the initial iPSC cultures, reached nearly 20% of the total culture. This was greater than the relative number of progenitor cells produced from human-skin-fibroblast-derived iPSCs hFib-iPSCs or from the spontaneous differentiation groups P<0.05, as assessed by flow cytometry analysis. These induced cells expressed hematopoietic transcription factors TAL-1 and SCL. They developed into various hematopoietic colonies when exposed to semisolid media with hematopoietic cytokines such as EPO and G-CSF. Hematopoietic cell lineages were identified by phenotype analysis with Wright-Giemsa staining. The endothelial potential of the cells was also verified by the confirmation of the formation of vascular tube-like structures and the expression of endothelial-specific markers CD31 and VE-CADHERIN. Efficient induction of CD34+ progenitor cells, which retain hematopoietic and endothelial cell potential with defined factors, provides an opportunity to obtain patient-specific cells for iPSC therapy and a useful model for the study of the mechanisms of hematopoiesis and drug screening.



Autor: Yulin Xu, Lizhen Liu, Lifei Zhang, Shan Fu, Yongxian Hu, Yingjia Wang, Huarui Fu, Kangni Wu, Haowen Xiao, Senquan Liu, Xiaohong Y

Fuente: http://plos.srce.hr/



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