Human lymphoblastoid B-cell lines reprogrammed to EBV-free induced pluripotent stem cells

Blood. 2011 Aug 18;118(7):1797-800. doi: 10.1182/blood-2011-01-332064. Epub 2011 Jun 27.

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.

MeSH terms

  • B-Lymphocytes / cytology*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / virology*
  • Cell Differentiation
  • Cell Line
  • Epstein-Barr Virus Nuclear Antigens / genetics
  • Genetic Vectors / genetics
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / isolation & purification*
  • Herpesvirus 4, Human / physiology
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / virology*
  • Transcription Factors / metabolism
  • Transfection

Substances

  • Epstein-Barr Virus Nuclear Antigens
  • Transcription Factors
  • EBV-encoded nuclear antigen 1