Induced pluripotent stem cells from GMP-grade hematopoietic progenitor cells and mononuclear myeloid cells

We examined the feasibility of reprogramming mobilized GMP-grade hematopoietic progenitor cells (HPCs) and peripheral blood mononuclear cells (PBMCs) and tested the pluripotency of derived iPS clones.Ectopic expression of OCT4, SOX2, KLF4, and c-MYC in HPCs and PBMCs resulted in rapid iPSC derivation. Long-term time-lapse imaging revealed efficient iPSC growth under serum- and feeder-free conditions with frequent mitotic events. HPC- and PBMC-derived iPS cells expressed pluripotency-associated markers, including SSEA-4, TRA-1-60, and NANOG. The global gene-expression profiles demonstrated the induction of endogenous pluripotent genes, such as LIN28, TERT, DPPA4, and PODXL, in derived iPSCs. iPSC clones from blood and other cell sources showed similar ultrastructural morphologies and genome-wide gene-expression profiles. On spontaneous and guided differentiation, HPC- and PBMC-derived iPSCs were differentiated into cells of three germ layers, including insulin-producing cells through endodermal lineage, verifying the pluripotency of the blood-derived iPSC clones.Because the use of blood cells allows minimally invasive tissue procurement under GMP conditions and rapid cellular reprogramming, mobilized HPCs and unmobilized PBMCs would be ideal somatic cell sources for clinical-grade iPSC derivation, especially from diabetes patients complicated by slow-healing wounds.Because embryonic stem (ES) cells can self-renew indefinitely and differentiate into any cell present in the adult organism, ES cells provide a unique platform for regenerative medicine approaches. In early 2009, the US Food and Drug Administration (FDA) approved the first clinical trial using ES cells in patients with spinal cord injuries. Although the FDA temporarily placed the trial on hold because of concerns over the risk of ES-derived cyst formation, the clinical hold was lifted, and the first patient for ES cell treatment was enrolled by Geron in late 2010 [1]. The use of ES-derived, terminally diff