title: Human lymphoblastoid B-cell lines reprogrammed to EBV-free induced pluripotent stem cells.
abstract: Generation of patient-specific induced pluripotent cells (iPSCs) holds great promise for regenerative medicine. Epstein-Barr virus immortalized lymphoblastoid B-cell lines (LCLs) can be generated from a minimal amount of blood and are banked worldwide as cellular reference material for immunologic or genetic analysis of pedigreed study populations. We report the generation of iPSCs from 2 LCLs (LCL-iPSCs) via a feeder-free episomal method using a cocktail of transcription factors and small molecules. LCL-derived iPSCs exhibited normal karyotype, expressed pluripotency markers, lost oriP/EBNA-1 episomal vectors, generated teratomas, retained donor identity, and differentiated in vitro into hematopoietic, cardiac, neural, and hepatocyte-like lineages. Significantly, although the parental LCLs express viral EBNA-1 and other Epstein-Barr virus latency-related elements for their survival, their presence was not detectable in LCL-iPSCs. Thus, reprogramming LCLs could offer an unlimited source for patient-specific iPSCs.
authors.affiliation: Cellular Dynamics International Inc, Madison, WI 53711-1018, USA. drajesh@cellulardynamics.com
authors.forename: Deepika
authors.initials: D
authors.lastname: Rajesh
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Dickerson
authors.forename: Junying
authors.initials: J
authors.lastname: Yu
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Brown
authors.forename: James A
authors.initials: JA
authors.lastname: Thomson
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Seay
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism / Q000821:virology*; D002454:Cell Differentiation; D002460:Cell Line; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000821:virology*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
chemical_list: D019309:Epstein-Barr Virus Nuclear Antigens; D014157:Transcription Factors; C417029:EBV-encoded nuclear antigen 1