The efficient commitment of a specialized cell type from induced pluripotent stem cells (iPSCs) without contamination from\r\nunknown substances is crucial to their use in clinical applications. Here, we propose that CD34+ progenitor cells, which\r\nretain hematopoietic and endothelial cell potential, could be efficiently obtained from iPSCs derived from human bone\r\nmarrow mesenchymal stem cells (hBMMSC-iPSCs) with defined factors. By treatment with a cocktail containing mesodermal,\r\nhematopoietic, and endothelial inducers (BMP4, SCF, and VEGF, respectively) for 5 days, hBMMSC-iPSCs expressed the\r\nmesodermal transcription factors Brachyury and GATA-2 at higher levels than untreated groups (P,0.05). After culturing\r\nwith another hematopoietic and endothelial inducer cocktail, including SCF, Flt3L, VEGF and IL-3, for an additional 7ââ?¬â??9 days,\r\nCD34+ progenitor cells, which were undetectable in the initial iPSC cultures, reached nearly 20% of the total culture. This\r\nwas greater than the relative number of progenitor cells produced from human-skin-fibroblast-derived iPSCs (hFib-iPSCs) or\r\nfrom the spontaneous differentiation groups (P,0.05), as assessed by flow cytometry analysis. These induced cells\r\nexpressed hematopoietic transcription factors TAL-1 and SCL. They developed into various hematopoietic colonies when\r\nexposed to semisolid media with hematopoietic cytokines such as EPO and G-CSF. Hematopoietic cell lineages were\r\nidentified by phenotype analysis with Wright-Giemsa staining. The endothelial potential of the cells was also verified by the\r\nconfirmation of the formation of vascular tube-like structures and the expression of endothelial-specific markers CD31 and\r\nVE-CADHERIN. Efficient induction of CD34+ progenitor cells, which retain hematopoietic and endothelial cell potential with\r\ndefined factors, provides an opportunity to obtain patient-specific cells for iPSC therapy and a useful model for the study of\r\nthe mechanisms of hematopoiesis and drug screening.
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