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Updated: Jan 30, 2026

The Dimethylnitrosamine Induced Liver Fibrosis Model in the Rat
Published on: June 17, 2016
Hepatocyte Growth Factor-Secreting Mesothelial Cell Sheets Suppress Progressive Fibrosis in a Rat Model of CKD
Masatoshi Oka1,2, Sachiko Sekiya2, Ryoichi Sakiyama3
1Department of Medicine, Kidney Center.
Insights
Cell sheet therapy using hepatocyte growth factor (HGF) transgenic mesothelial cells shows promise for treating kidney fibrosis. This novel approach effectively suppressed fibrosis and maintained renal blood flow in preclinical models.
Area of Science:
- Nephrology
- Regenerative Medicine
- Biotechnology
Background:
- Hepatocyte growth factor (HGF) exhibits antifibrotic, angiogenic, and vasodilatory properties.
- Systemic HGF administration is not a viable strategy for managing chronic kidney disease (CKD) interstitial fibrosis.
- Novel therapeutic approaches are needed to combat progressive kidney fibrosis.
Purpose of the Study:
- To investigate the efficacy of HGF-transgenic mesothelial cell sheet therapy for kidney fibrosis.
- To compare HGF-transgenic cell sheets with other interventions in a rat model of kidney fibrosis.
Main Methods:
- Human mesothelial cells genetically engineered to produce HGF were cultured into cell sheets.
- Rats with unilateral ureteral obstruction (UUO) underwent transplantation of HGF-transgenic cell sheets to the kidney surface.
- Interventions included HGF-transgenic cell sheets (kidney or thigh), non-transgenic cell sheets (kidney), no sheets, or HGF injections.
Main Results:
- HGF-transgenic cell sheets transplanted to the kidney significantly suppressed myofibroblast induction and collagen deposition for 28 days.
- Other tested interventions did not demonstrate significant antifibrotic effects.
- HGF-secreting cell sheets preserved peritubular capillaries and maintained renal blood flow.
Conclusions:
- Cell sheet therapy utilizing HGF-transgenic mesothelial cells represents a novel and promising strategy for inhibiting progressive kidney fibrosis.
- This approach holds potential for therapeutic applications in chronic kidney disease (CKD).
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.
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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