No evidence of neoplastic transformation after proliferation of transplanted hepatocytes

Laconi S et al. (2006) Liver repopulation by transplanted hepatocytes and risk of hepatocellular carcinoma. Transplantation 82: 1319–1323

Hepatocyte transplantation is a feasible therapeutic strategy for patients with end-stage liver disease, but has poor efficacy because transplanted cells generally do not replace much of the recipient's liver. Laconi and colleagues investigated whether preconditioning of recipient animals with retrorsine (which suppresses proliferation of endogenous hepatocytes) might facilitate the clonal expansion of transplanted cells.

Rats engineered to lack CD26 expression on their hepatocytes received injections of either 30 mg/kg body weight retrorsine (n = 16), or saline (n = 16) once weekly for 2 weeks. After an additional 2 weeks, all rats received infusions of 2 × 10⁶ CD26⁺ hepatocytes via the portal vein (95% hepatocytes, 85–95% viable cells). After 18 months, six rats from each group were killed, the remaining rats were killed at 24 months and their livers analyzed.

There was extensive, sustained replacement of the host liver in retrorsine-treated rats killed at 18 months and 24 months (91 ± 7% and 87 ± 5% of the host liver replaced, respectively), but no substantial proliferation of donor hepatocyte cells in control rats. Donor-derived hepatocytes were normal on histologic evaluation. Liver integrity and function were also normal in retrorsine-treated rats—demonstrated by similar levels of total proteins, alanine aminotransferase, total bilirubin, and alkaline phosphatase—compared with control rats.

Although the transplanted cells underwent multiple mitotic divisions, there was no evidence of neoplastic transformation in transplanted hepatocytes from control or retrorsine-treated rats over 2 years. These encouraging results suggest that host-liver preconditioning might improve the efficiency of hepatocyte transplantation in humans.