Amelioration of Cisplatin-Induced Acute Renal Injury by Renal Progenitor-Like Cells Derived from the Adult Rat Kidney

Cell Transplantation

Article

Hitoshi Sugiyama¹  Takeshi Sugaya²  Hiroyuki Kitayama³  Yuki Takazawa³  Masaru Kinomura³  Kumiko Hirokoshi³  Shinji Kitamura³  Yasushi Yamasaki³  Tatsuyo Nasu³  Katsuyuki Tanabe³  Yohei Maeshima³  Kunihiro Ichinose³  Hirofumi Makino³ 

[1] Center for Chronic Kidney Disease and Peritoneal Dialysis, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan;Corneal Transplant Center, Tokyo Dental College, Chiba, Japan;Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan;

关键词: Renal progenitor cell;    Cisplatin;    Tubular epithelium;    Apoptosis;    Proliferation;   

DOI  :  10.3727/000000008783907008

 received in 2007-02-05, accepted in 2007-09-30,  发布年份 2008

来源: Sage Journals

【 摘 要 】

The replacement of a necrotic tubular epithelium with functional tubular epithelial cells is required for recovery from acute renal failure (ARF). A rat renal progenitor-like (rKS56) cell line was recently established derived from the S3 segment of renal proximal tubules. The therapeutic efficacy of rKS56 cells was examined in a rat model of cisplatin-induced ARF. rKS56-lacZ cells expressing β-galactosidase were injected into SD rats either at the subcapsule of the left kidney (rKS-SC) or via the left renal artery (rKS-IA) 2 days after the injection of cisplatin. Bluo-gal(+) rKS56-lacZ cells were observed in the subcapsule in the rKS-SC group on day 5, and were further increased in number on day 9, accompanied by partial distribution in the corticomedullary junction, but not in the rKS-IA group. A portion of Bluo-gal(+) cells coexpressed Ki-67, aquaporin-1, hepatocyte growth factor (HGF), and c-Met. rKS-SC treatment significantly improved the tubular injury scores, ameliorated tubular cell apoptosis, and induced cell proliferation. The renal function also significantly improved in the rKS-SC group on day 5. These results demonstrate that locally implanted rKS56 cells could differentiate into tubular epithelial cells, thereby accelerating the recovery from tubular injury, most likely by producing tubular trophic factors. These results suggest the therapeutic potential of this novel approach for patients with end-stage renal failure.

【 授权许可】

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