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

Seiga Ohmine, Allan B. Dietz, Michael C. Deeds, Katherine A. Hartjes, David R. Miller, Tayaramma Thatava, Toshie Sakuma, Yogish C. Kudva, Yasuhiro Ikeda

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Introduction. The induced pluripotent stem cell (iPSC) technology allows generation of patient-specific pluripotent stem cells, thereby providing a novel cell-therapy platform for severe degenerative diseases. One of the key issues for clinical-grade iPSC derivation is the accessibility of donor cells used for reprogramming. Methods. 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Article number46
JournalStem Cell Research and Therapy
Volume2
Issue number6
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Cell Biology

Fingerprint Dive into the research topics of 'Induced pluripotent stem cells from GMP-grade hematopoietic progenitor cells and mononuclear myeloid cells'. Together they form a unique fingerprint.

  • Cite this