Successful disease-specific induced pluripotent stem cell generation from patients with kidney transplantation

The feasibility of iPS cell generation from patients with a history of ESRD was investigated using lentiviral vectors expressing pluripotency-associated factors.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.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.The prevalence of chronic kidney disease and end-stage renal disease (ESRD) is increasing worldwide [1]. Simultaneously, the total Medicare cost of ESRD has risen from $12.2 billion in 2000 to $39.5 billion in 2010 [1]. ESRD is incurable, requiring hemodialysis or preferably renal transplantation. These therapies are associated with considerable limitations, however, including the shortage of available donor organs and a lifelong immunosuppressive regimen [2]. Moreover, despite significant improvement in 1-year kidney allograft survival, the rate of chronic graft loss after the first year remains substantial [3].The most common causes of ESRD in the United States are diabetes and hypertension [4], while the incidence of nondiabetic ESRD, such as glomerular diseases and cystic diseases, are increasing. Autosomal-domi