Hepatocyte Growth Factor-Secreting Mesothelial Cell Sheets Suppress Progressive Fibrosis in a Rat Model of CKD

分泌肝细胞生长因子的间皮细胞片可抑制 CKD 大鼠模型中的进行性纤维化

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作者:Masatoshi Oka, Sachiko Sekiya, Ryoichi Sakiyama, Tatsuya Shimizu, Kosaku Nitta

Background

Although hepatocyte growth factor (HGF) has antifibrotic effects and is involved in angiogenesis and vasodilation, systemic administration of HGF to prevent kidney fibrosis is not a feasible strategy for suppressing interstitial fibrosis in patients with CKD.

Conclusions

These findings suggest that cell sheet therapy is a novel and promising strategy for inhibiting progressive fibrosis in CKD.

Methods

We investigated a novel therapy involving HGF transgenic cell sheets grown in culture from human mesothelial cells and administered to rats with unilateral ureteral obstruction (UUO). We compared progression of fibrosis in rats with UUO that received one of five interventions: HGF-transgenic mesothelial cell sheets transplanted to the kidney surface, HGF-transgenic mesothelial cell sheets transplanted to thigh, mesotherial cell sheets transplanted to kidney, no sheets, or HGF injections.

Results

HGF transgenic cell sheets transplanted to the kidney strongly suppressed the induction of myofibroblasts and collagen in the kidney for 28 days; other interventions did not. Additionally, the HGF-secreting cell sheets ameliorated loss of peritubular capillaries and maintained renal blood flow. Conclusions: These findings suggest that cell sheet therapy is a novel and promising strategy for inhibiting progressive fibrosis in CKD.

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