Background

Rapid regeneration of the remnant liver after extended partial hepatectomy or reduced size liver transplantation is essential to prevent small-for-size syndrome (SFSS). We hypothesize that mobilization of endogenous stem cells with AMD3100, an antagonist of CXCR4, and low-dose FK506 may improve regeneration in both of these clinical scenarios.

Methods

Male Lewis rats (220-250g) underwent 85% partial hepatectomy (PH) or reduced size (30-35%) liver transplantation (LT). Animals from both groups were randomized to receive subcutaneous injections of saline or dual drug therapy (AMD3100 1mg/kg/day and FK506 0.1mg/kg/day) immediately after surgery and on postoperative days (POD) 1, 2, and 3. Animals were sacrificed on POD 3 or 7, and blood samples were collected to examine hepatocellular damage. Liver tissues were sampled to evaluate weight and regeneration rate.

Results

All animals survived following PH. The dual drug therapy increased CD133+ stem cells in the liver, enhanced liver regeneration, and reduced liver injury at 3 and 7 days after PH. In the LT model, 25% of saline-treated animals died within 7 days, while animals treated with dual drugs survived. Serum levels of AST, ALT, and total bilirubin were significantly higher in animals treated with saline than in animals treated with dual drugs. Quantitative histological analysis demonstrated enhanced hepatocyte proliferation (Ki67+) in animals treated with dual drug therapy.

Conclusions

Mobilization of endogenous stem cells with AMD3100 plus low-dose FK506 results in improved regeneration of the remnant liver after extended hepatectomy and partial liver transplantation, and minimizes SFSS in rats.

CITATION INFORMATION: Chen M, Zhai R, Qi L, Cameron A, Philosophe B, Sun Z. Improved Regeneration of the Remnant Liver After Extended Hepatectomy or Partial Liver Transplantation by Pharmacologic Mobilization of Endogenous Stem Cells in Rats. Am J Transplant. 2016;16 (suppl 3).

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