title: A comparison of non-integrating reprogramming methods.
abstract: Human induced pluripotent stem cells (hiPSCs) are useful in disease modeling and drug discovery, and they promise to provide a new generation of cell-based therapeutics. To date there has been no systematic evaluation of the most widely used techniques for generating integration-free hiPSCs. Here we compare Sendai-viral (SeV), episomal (Epi) and mRNA transfection mRNA methods using a number of criteria. All methods generated high-quality hiPSCs, but significant differences existed in aneuploidy rates, reprogramming efficiency, reliability and workload. We discuss the advantages and shortcomings of each approach, and present and review the results of a survey of a large number of human reprogramming laboratories on their independent experiences and preferences. Our analysis provides a valuable resource to inform the use of specific reprogramming methods for different laboratories and different applications, including clinical translation.
authors.affiliation: 1] Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
authors.forename: Thorsten M
authors.initials: TM
authors.lastname: Schlaeger
authors.affiliation: Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Daheron
authors.affiliation: Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Brickler
authors.affiliation: Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Entwisle
authors.affiliation: Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Karrie
authors.initials: K
authors.lastname: Chan
authors.affiliation: Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Amelia
authors.initials: A
authors.lastname: Cianci
authors.affiliation: Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: DeVine
authors.affiliation: Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Andrew
authors.identifier: 0000000322584329
authors.initials: A
authors.lastname: Ettenger
authors.affiliation: Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Fitzgerald
authors.affiliation: Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Godfrey
authors.affiliation: Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Dipti
authors.initials: D
authors.lastname: Gupta
authors.affiliation: Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Jade
authors.initials: J
authors.lastname: McPherson
authors.affiliation: Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Prerana
authors.initials: P
authors.lastname: Malwadkar
authors.affiliation: Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Manav
authors.initials: M
authors.lastname: Gupta
authors.affiliation: Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Blair
authors.initials: B
authors.lastname: Bell
authors.affiliation: 1] Center for Epigenetics and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Akiko
authors.initials: A
authors.lastname: Doi
authors.affiliation: Center for Epigenetics and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Namyoung
authors.initials: N
authors.lastname: Jung
authors.affiliation: Center for Epigenetics and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
authors.forename: Maureen S
authors.initials: MS
authors.lastname: Lynes
authors.affiliation: Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Brookes
authors.affiliation: 1] Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Anne B C
authors.initials: AB
authors.lastname: Cherry
authors.affiliation: The Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Didem
authors.initials: D
authors.lastname: Demirbas
authors.affiliation: 1] Harvard Stem Cell Institute, Cambridge, Massachusetts, USA. [2] Broad Institute, Cambridge, Massachusetts, USA.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Tsankov
authors.affiliation: 1] Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
authors.forename: Leonard I
authors.initials: LI
authors.lastname: Zon
authors.affiliation: 1] Harvard Stem Cell Institute, Cambridge, Massachusetts, USA. [2] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Lee L
authors.initials: LL
authors.lastname: Rubin
authors.affiliation: Center for Epigenetics and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Feinberg
authors.affiliation: 1] Harvard Stem Cell Institute, Cambridge, Massachusetts, USA. [2] Broad Institute, Cambridge, Massachusetts, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Meissner
authors.affiliation: 1] Harvard Stem Cell Institute, Cambridge, Massachusetts, USA. [2] Broad Institute, Cambridge, Massachusetts, USA. [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA. [4] Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Cowan
authors.affiliation: 1] Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Harvard Stem Cell Institute, Cambridge, Massachusetts, USA. [3] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA. [4] Howard Hughes Medical Institute, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: George Q
authors.initials: GQ
authors.lastname: Daley
mesh_terms: D065150:Cellular Reprogramming; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*