TY - JOUR
T1 - Successful disease-specific induced pluripotent stem cell generation from patients with kidney transplantation
AU - Thatava, Tayaramma
AU - Armstrong, Adam S.
AU - De Lamo, Josep
AU - Edukulla, Ramakrishna
AU - Khan, Yulia
AU - Sakuma, Toshie
AU - Ohmine, Seiga
AU - Sundsbak, Jamie L.
AU - Harris, Peter C.
AU - Kudva, Yogish C.
AU - Ikeda, Yasuhiro
N1 - Funding Information:
The present work was supported by the Mayo Foundation, Marriott Individualized Medicine Award, Eisenberg Stem Cell Trust, Bernard and Edith Waterman Pilot Grants (YI), Marriott Specialized Workforce Development Award in Individualized Medicine (TT), and National Institutes of Health (DK 85516 to YCK). The Mayo Translational PKD Center (DK090728) undertook the PKD1 mutation analysis.
PY - 2011
Y1 - 2011
N2 - Introduction. 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.
AB - Introduction. 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.
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U2 - 10.1186/scrt89
DO - 10.1186/scrt89
M3 - Article
C2 - 22142803
AN - SCOPUS:84855683134
SN - 1757-6512
VL - 2
JO - Stem Cell Research and Therapy
JF - Stem Cell Research and Therapy
IS - 6
M1 - 48
ER -