Amelioration of cisplatin-induced acute renal injury by renal progenitor-like cells derived from the adult rat kidney.
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 3-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.
Kinomura
Masaru
M
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Kitamura
Shinji
S
Tanabe
Katsuyuki
K
Ichinose
Kunihiro
K
Hirokoshi
Kumiko
K
Takazawa
Yuki
Y
Kitayama
Hiroyuki
H
Nasu
Tatsuyo
T
Sugiyama
Hitoshi
H
Yamasaki
Yasushi
Y
Sugaya
Takeshi
T
Maeshima
Yohei
Y
Makino
Hirofumi
H
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D017209:Apoptosis; D051398:Aquaporin 1 / Q000096:biosynthesis; D002460:Cell Line; D049109:Cell Proliferation; D002945:Cisplatin / Q000633:toxicity; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis; D015552:Injections, Intralesional; D019394:Ki-67 Antigen / Q000096:biosynthesis; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology
D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D051398:Aquaporin 1; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D002945:Cisplatin