title: Advanced feeder-free generation of induced pluripotent stem cells directly from blood cells.
abstract: Generation of validated human induced pluripotent stem cells (iPSCs) for biobanking is essential for exploring the full potential of iPSCs in disease modeling and drug discovery. Peripheral blood mononuclear cells (PBMCs) are attractive targets for reprogramming, because blood is collected by a routine clinical procedure and is a commonly stored material in biobanks. Generation of iPSCs from blood cells has previously been reported using integrative retroviruses, episomal Sendai viruses, and DNA plasmids. However, most of the published protocols require expansion and/or activation of a specific cell population from PBMCs. We have recently collected a PBMC cohort from the Finnish population containing more than 2,000 subjects. Here we report efficient generation of iPSCs directly from PBMCs in feeder-free conditions in approximately 2 weeks. The produced iPSC clones are pluripotent and transgene-free. Together, these properties make this novel method a powerful tool for large-scale reprogramming of PBMCs and for iPSC biobanking.
authors.affiliation: Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, Helsinki, Finland; Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan; Department of Chronic Disease Prevention and Public Health Genomics Unit, THL Biobank, National Institute for Health and Welfare (THL), Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Ras
authors.initials: R
authors.lastname: Trokovic
authors.affiliation: Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, Helsinki, Finland; Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan; Department of Chronic Disease Prevention and Public Health Genomics Unit, THL Biobank, National Institute for Health and Welfare (THL), Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Jere
authors.initials: J
authors.lastname: Weltner
authors.affiliation: Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, Helsinki, Finland; Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan; Department of Chronic Disease Prevention and Public Health Genomics Unit, THL Biobank, National Institute for Health and Welfare (THL), Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Ken
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, Helsinki, Finland; Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan; Department of Chronic Disease Prevention and Public Health Genomics Unit, THL Biobank, National Institute for Health and Welfare (THL), Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Manami
authors.initials: M
authors.lastname: Ohtaka
authors.affiliation: Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, Helsinki, Finland; Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan; Department of Chronic Disease Prevention and Public Health Genomics Unit, THL Biobank, National Institute for Health and Welfare (THL), Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Mahito
authors.initials: M
authors.lastname: Nakanishi
authors.affiliation: Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, Helsinki, Finland; Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan; Department of Chronic Disease Prevention and Public Health Genomics Unit, THL Biobank, National Institute for Health and Welfare (THL), Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, Helsinki, Finland; Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan; Department of Chronic Disease Prevention and Public Health Genomics Unit, THL Biobank, National Institute for Health and Welfare (THL), Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Jalanko
authors.affiliation: Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, Helsinki, Finland; Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan; Department of Chronic Disease Prevention and Public Health Genomics Unit, THL Biobank, National Institute for Health and Welfare (THL), Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Otonkoski
authors.affiliation: Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, University of Helsinki, Helsinki, Finland; Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan; Department of Chronic Disease Prevention and Public Health Genomics Unit, THL Biobank, National Institute for Health and Welfare (THL), Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland aija.kyttala@thl.fi.
authors.forename: Aija
authors.initials: A
authors.lastname: Kyttälä
mesh_terms: D005260:Female; D005387:Finland; D005822:Genetic Vectors; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000378:metabolism; D008297:Male
keywords: Cell banking; Induced pluripotent stem cells; Nuclear reprogramming; Sendai virus