Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Stem Cell Res Ther. 2011 Dec 6;2(6):48. doi: 10.1186/scrt89.
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.
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.
终末期肾病（ESRD）是一个主要的公共卫生问题。尽管肾移植是一种可行的治疗选择，但这种疗法存在显著的局限性，包括供体器官短缺。诱导多能干细胞（iPS）技术可以从患者身上获得特异性多能干细胞，为 ESRD 患者的肾脏替代治疗提供了一种可能的替代方式。
利用表达多能性相关因子的慢病毒载体，研究了从有 ESRD 病史的患者中生成 iPS 细胞的可行性。
本文首次报道了从患有常染色体显性多囊肾病（ADPKD）、系统性红斑狼疮或威尔姆斯瘤和 ESRD 的肾移植受者中生成 iPS 细胞。在无饲养层条件下，OCT4、SOX2、KLF4 和 c-MYC 的慢病毒转导导致皮肤衍生角质形成细胞的重编程。角质形成细胞来源的 iPS 细胞表现出人类胚胎干细胞的特性，包括形态、生长特性、多能性基因和表面标志物的表达、自发分化和畸胎瘤形成。ADPKD 患者的所有 iPS 细胞克隆均保留 PKD1 基因外显子 41 中 W3842X 突变。
我们的结果表明，从有 ESRD 病史、PKD1 基因突变或慢性免疫抑制史的患者中成功生成了 iPS 细胞。ADPKD 等常染色体肾脏疾病的 iPS 细胞将为体外研究患者特异性疾病发病机制提供独特的机会。
