title: Successful disease-specific induced pluripotent stem cell generation from patients with kidney transplantation.
abstract: BACKGROUND
  End-stage renal disease (ESRD) is a major public health problem. Although kidney transplantation is a viable therapeutic option, this therapy is associated with significant limitations, including a shortage of donor organs. Induced pluripotent stem (iPS) cell technology, which allows derivation of patient-specific pluripotent stem cells, could provide a possible alternative modality for kidney replacement therapy for patients with ESRD.
  
  
  METHODS
  The feasibility of iPS cell generation from patients with a history of ESRD was investigated using lentiviral vectors expressing pluripotency-associated factors.
  
  
  RESULTS
  In the present article we report, for the first time, generation of iPS cells from kidney transplant recipients with a history of autosomal-dominant polycystic kidney disease (ADPKD), systemic lupus erythematosus, or Wilms tumor and ESRD. Lentiviral transduction of OCT4, SOX2, KLF4 and c-MYC, under feeder-free conditions, resulted in reprogramming of skin-derived keratinocytes. Keratinocyte-derived iPS cells exhibited properties of human embryonic stem cells, including morphology, growth properties, expression of pluripotency genes and surface markers, spontaneous differentiation and teratoma formation. All iPS cell clones from the ADPKD patient retained the conserved W3842X mutation in exon 41 of the PKD1 gene.
  
  
  CONCLUSIONS
  Our results demonstrate successful iPS cell generation from patients with a history of ESRD, PKD1 gene mutation, or chronic immunosuppression. iPS cells from autosomal kidney diseases, such as ADPKD, would provide unique opportunities to study patient-specific disease pathogenesis in vitro.
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Tayaramma
authors.initials: T
authors.lastname: Thatava
authors.forename: Adam S
authors.initials: AS
authors.lastname: Armstrong
authors.forename: Josep Genebriera
authors.initials: JG
authors.lastname: De Lamo
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Edukulla
authors.forename: Yulia Krotova
authors.initials: YK
authors.lastname: Khan
authors.forename: Toshie
authors.initials: T
authors.lastname: Sakuma
authors.forename: Seiga
authors.initials: S
authors.lastname: Ohmine
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Sundsbak
authors.forename: Peter C
authors.initials: PC
authors.lastname: Harris
authors.forename: Yogish C
authors.initials: YC
authors.lastname: Kudva
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
mesh_terms: D002454:Cell Differentiation; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000166:cytology; D005822:Genetic Vectors / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D015603:Keratinocytes / Q000166:cytology; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy; D016030:Kidney Transplantation; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D009154:Mutation; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D050396:TRPP Cation Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; D016271:Proto-Oncogene Proteins c-myc; D055748:SOXB1 Transcription Factors; D050396:TRPP Cation Channels; C000715467:KLF4 protein, human