Direct generation of induced pluripotent stem cells from human nonmobilized 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 nonmobilized 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 quite similar to human embryonic stem cells with regard 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 × 10(5) 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 nonmobilized PB, with its relative efficiency and ease of harvesting, could enable the therapeutic use of patient-specific pluripotent stem cells.
Kunisato
Atsushi
A
Frontier Laboratory, Kyowa Hakko Kirin Co. Ltd., Tokyo, Japan.
Wakatsuki
Mariko
M
Shinba
Haruna
H
Ota
Toshio
T
Ishida
Isao
I
Nagao
Kenji
K
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001773:Blood Cells / Q000166:cytology*; D001854:Bone Marrow Cells / Q000166:cytology; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000235:genetics; D002999:Clone Cells; D019175:DNA Methylation / Q000235:genetics; D015321:Gene Rearrangement / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D014019:Tissue Donors
D015415:Biomarkers; D007143:Immunoglobulin Heavy Chains; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D016693:Receptors, Antigen, T-Cell, alpha-beta