title: Feeder-independent derivation of induced-pluripotent stem cells from peripheral blood endothelial progenitor cells.
abstract: Induced-pluripotent stem cells (iPSCs) are a potential alternative cell source in regenerative medicine, which includes the use of differentiated iPSCs for cell therapies to treat coronary artery and/or peripheral arterial diseases. Late-outgrowth endothelial progenitor cells (late-EPCs) are a unique primary cell present in peripheral blood that exhibit high proliferative capacity, are being used in a wide variety of clinical trials, and have the ability to differentiate into mature endothelial cells. The objective of this study was to reprogram peripheral blood-derived late-EPCs to a pluripotent state under feeder-free and defined culture conditions. Late-EPCs that were retrovirally transduced with OCT4, SOX2, KLF4, c-MYC, and iPSC colonies were derived in feeder-free and defined media conditions. EPC-iPSCs expressed pluripotent markers, were capable of differentiating to cells from all three germ-layers, and retained a normal karyotype. Transcriptome analyses demonstrated that EPC-iPSCs exhibit a global gene expression profile similar to human embryonic stem cells (hESCs). We have generated iPSCs from late-EPCs under feeder-free conditions. Thus, peripheral blood-derived late-outgrowth EPCs represent an alternative cell source for generating iPSCs.
authors.affiliation: Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: Wing Y
authors.initials: WY
authors.lastname: Chang
authors.forename: Jessie R
authors.initials: JR
authors.lastname: Lavoie
authors.forename: Sarah Y
authors.initials: SY
authors.lastname: Kwon
authors.forename: Zhaoyi
authors.initials: Z
authors.lastname: Chen
authors.forename: Janet L
authors.initials: JL
authors.lastname: Manias
authors.forename: John
authors.initials: J
authors.lastname: Behbahani
authors.forename: Vicki
authors.initials: V
authors.lastname: Ling
authors.forename: Rita A
authors.initials: RA
authors.lastname: Kandel
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Stewart
authors.forename: William L
authors.initials: WL
authors.lastname: Stanford
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D065150:Cellular Reprogramming; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D061252:Feeder Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D007621:Karyotyping; D000090062:Kruppel-Like Factor 4; D012190:Retroviridae / Q000235:genetics; D059467:Transcriptome / Q000235:genetics
chemical_list: D015415:Biomarkers; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4