title: Induced pluripotent stem cells from GMP-grade hematopoietic progenitor cells and mononuclear myeloid cells.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Molecular Medicine, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Seiga
authors.initials: S
authors.lastname: Ohmine
authors.forename: Allan B
authors.initials: AB
authors.lastname: Dietz
authors.forename: Michael C
authors.initials: MC
authors.lastname: Deeds
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hartjes
authors.forename: David R
authors.initials: DR
authors.lastname: Miller
authors.forename: Tayaramma
authors.initials: T
authors.lastname: Thatava
authors.forename: Toshie
authors.initials: T
authors.lastname: Sakuma
authors.forename: Yogish C
authors.initials: YC
authors.lastname: Kudva
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy; D065150:Cellular Reprogramming; D020869:Gene Expression Profiling; D005822:Genetic Vectors / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000637:transplantation; D000090062:Kruppel-Like Factor 4; D016086:Lentivirus / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D000071317:Nanog Homeobox Protein; D019636:Neurodegenerative Diseases / Q000628:therapy; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D055746:Stage-Specific Embryonic Antigens / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D018398:Homeodomain Proteins; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D011509:Proteoglycans; D055746:Stage-Specific Embryonic Antigens; C107064:TRA-1-60 antigen, human; C066584:stage-specific embryonic antigen-4
references.citation: Cell Stem Cell. 2010 Jul 2;7(1):20-4
references.pmid: 20621045
references.citation: Cell Res. 2011 Mar;21(3):518-29
references.pmid: 21243013
references.citation: J Virol. 2001 Jun;75(12):5448-56
references.pmid: 11356951
references.citation: Int Immunol. 2011 Jan;23(1):65-74
references.pmid: 21135032
references.citation: Science. 2008 Aug 1;321(5889):699-702
references.pmid: 18276851
references.citation: Blood. 2011 Apr 7;117(14):e109-19
references.pmid: 21296996
references.citation: Blood. 2009 Aug 20;114(8):1461-8
references.pmid: 19471016
references.citation: Cell Stem Cell. 2009 Oct 2;5(4):434-41
references.pmid: 19796623
references.citation: Exp Hematol. 2010 Feb;38(2):154-62
references.pmid: 19922768
references.citation: Nature. 2009 Apr 9;458(7239):771-5
references.pmid: 19252477
references.citation: Nature. 2009 Apr 9;458(7239):766-70
references.pmid: 19252478
references.citation: Nature. 2007 Jul 19;448(7151):313-7
references.pmid: 17554338
references.citation: Nat Biotechnol. 2011 May;29(5):443-8
references.pmid: 21490602
references.citation: Nature. 2008 Jan 10;451(7175):141-6
references.pmid: 18157115
references.citation: Cell. 2006 Aug 25;126(4):663-76
references.pmid: 16904174
references.citation: Clin Transl Sci. 2009 Apr;2(2):118-26
references.pmid: 20161095
references.citation: Science. 2009 May 8;324(5928):797-801
references.pmid: 19325077
references.citation: Nature. 2007 Jul 19;448(7151):318-24
references.pmid: 17554336
references.citation: J Virol. 2006 Aug;80(15):7769-74
references.pmid: 16840358
references.citation: Blood. 2011 Aug 18;118(7):1801-5
references.pmid: 21628406
references.citation: J Biol Chem. 2008 Nov 14;283(46):31601-7
references.pmid: 18782754
references.citation: Cell Stem Cell. 2009 Oct 2;5(4):353-7
references.pmid: 19796614
references.citation: PLoS One. 2010 Jun 29;5(6):e11373
references.pmid: 20617191
references.citation: Nat Biotechnol. 2008 Nov;26(11):1276-84
references.pmid: 18931654
references.citation: Blood. 2009 May 28;113(22):5476-9
references.pmid: 19299331
references.citation: Circ Res. 2009 Sep 25;105(7):648-56
references.pmid: 19696409
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2883-8
references.pmid: 18287077
references.citation: Nat Protoc. 2010 Feb;5(2):371-82
references.pmid: 20134422
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15768-73
references.pmid: 19720998
references.citation: Blood. 2009 Dec 24;114(27):5473-80
references.pmid: 19797525
references.citation: Circulation. 2009 Aug 4;120(5):408-16
references.pmid: 19620500
references.citation: Blood. 2011 Aug 18;118(7):1797-800
references.pmid: 21708888
references.citation: Aging (Albany NY). 2012 Jan;4(1):60-73
references.pmid: 22308265
references.citation: J Physiol Biochem. 2011 Mar;67(1):141-4
references.pmid: 21246421
references.citation: Stem Cells. 2008 Jun;26(6):1537-46
references.pmid: 18450826
references.citation: Cell. 2011 Apr 15;145(2):178-81
references.pmid: 21496640
references.citation: Gene Ther. 2011 Mar;18(3):283-93
references.pmid: 21048796
references.citation: Cell. 2008 Apr 18;133(2):250-64
references.pmid: 18423197
references.citation: Cell. 2007 Nov 30;131(5):861-72
references.pmid: 18035408
references.citation: Cell Stem Cell. 2011 Apr 8;8(4):376-88
references.pmid: 21474102
references.citation: Stem Cells Dev. 2011 Jan;20(1):159-68
references.pmid: 20497033
references.citation: Cell Stem Cell. 2010 Jul 2;7(1):11-4
references.pmid: 20621043
references.citation: Science. 2007 Dec 21;318(5858):1917-20
references.pmid: 18029452
references.citation: Cell Stem Cell. 2010 Jul 2;7(1):15-9
references.pmid: 20621044