Direct generation of induced pluripotent stem cells from human non-mobilized blood

The use of induced pluripotent stem cells (iPSCs) is an exciting frontier in the study and treatment of human diseases through the generation of specific cell types. Here we show the derivation of iPSCs from human non-mobilized peripheral blood (PB) and bone marrow (BM) mononuclear cells (MNCs) by retroviral transduction of OCT3/4, SOX2, KLF4 and c-MYC. The PB- and BM-derived iPSCs were indistinguishable from human embryonic stem cells (hESCs) with respect to morphology, expression of surface antigens and pluripotency-associated transcription factors, global gene expression profiles and differentiation potential in vitro and in vivo. Infected PB and BM MNCs gave rise to iPSCs in the presence of several cytokines, although transduction efficiencies were not high. We found that 5×105 PB MNCs, which corresponds to less than 1 ml of PB, was enough for the generation of several iPSC colonies. Generation of iPSCs from MNCs of non-mobilized PB, with its relative efficiency and ease of harvesting, could enable the therapeutic use of patient-specific pluripotent stem cells. Gene expression profiling was performed in human BMMNCs, PBMNCs, hBMMNC derived iPS cell lines and hPBMNC derived iPS cell lines.