Amelioration of cisplatin-induced acute renal injury by renal progenitor-like cells derived from the adult rat kidney
Amelioration of cisplatin-induced acute renal injury by renal progenitor-like cells derived from the adult rat kidney
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DOI：
10.3727/000000008783907008
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Makino, Hirofumi
中科院分区：
文献类型：
--
作者：
Kinomura, Masaru;Kitamura, Shinji;Makino, Hirofumi
急性肾衰竭（ARF）恢复需要用功能性肾小管上皮细胞替代坏死的肾小管上皮。最近建立了源自肾近曲小管 S3 段的大鼠肾祖样 (rKS56) 细胞系。在顺铂诱导的 ARE 大鼠模型中检查 rKS56 细胞的治疗效果，在注射顺铂 2 天后，将表达 β-半乳糖苷酶的 rKS56-lacZ 细胞注射到 SD 大鼠的左肾下囊 (rKS-SC) 或通过左肾动脉 (rKS-IA)。 rKS-SC组第5天在被膜下可见Bluo-gal(+) rKS56-lacZ细胞，第9天数量进一步增加，并伴有部分分布于皮质髓质连接处，而rKS-IA组则没有。一部分 Bluo-gal(+) 细胞共表达 Ki-67、水通道蛋白-1、肝细胞生长因子 (HGF) 和 c-Met。 rKS-SC 治疗显着改善肾小管损伤评分，改善肾小管细胞凋亡，并诱导细胞增殖。第5天，rKS-SC组的肾功能也显着改善。这些结果表明，局部植入的rKS56细胞可以分化为肾小管上皮细胞，从而加速肾小管损伤的恢复，很可能是通过产生肾小管营养因子。这些结果表明这种新方法对终末期肾衰竭患者的治疗潜力。
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 ARE rKS56-lacZ cells expressing P-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.