Transcatheter hepatocyte transplantation: Preclinical studies of anatomic consequences in the portal vascular bed

Rationale and Objectives: Intrasplenic transplantation deposits hepatocytes in host hepatic sinusoids with amelioration of chronic liver failure and genetic deficiency states. Because portal resistance can be altered by intrasinusoidal transplanted cells, we examined whether hepatocyte recipients would develop deleterious portal hypertension or portosystemic collaterals. Methods: Syngeneic hepatocytes in suspension were transplanted into recipient rats by transcatheter injection into the splenic parenchyma. Subjects included recipients of 2×10⁷ hepatocytes representing approximately 3% of the host hepatic mass, recipients of 7.5×10⁷ hepatocytes representing approximately 12.5% of the host hepatic mass, normal control rats, and positive control rats with portal hypertension induced by partial portal vein constriction. Portal pressures were recorded with a sensitive transducer, portosystemic collaterals were demonstrated with direct splenoportography, and survival of transplanted cells was determined with an endogenous dipeptidyl peptidase IV reporter gene. Results: In normal rats, the portal pressure was 6.25±1.9 mm Hg with no portosystemic collaterals. By contrast, portal pressures were significantly increased in portal vein-constricted rats, 20.7±3.9 mm Hg (P<0.001), with extensive portosystemic collaterals. In hepatocyte recipients, portal hypertension observed during transcatheter cell injection but proved transient. When animals were examine dup to 16 weeks after hepatocyte transplantation, portal pressures were in the normal range (after 2×10⁷ cells, 7.5×2.6 mm Hg; after 7.5×10⁷ cells, 9.5±4.2 mm Hg, P=not significant). No portosystemic collaterals developed in hepatocyte recipients at various times up to 8 months after transplantation. Transplanted hepatocytes expressing the reporter gene were present in recipients with assimilation in host hepatic cords. Conclusion: Despite injection of a massive number of cells, transcatheter hepatocyte transplantation was devoid of any significant portal vascular alterations or toxicity in recipients. These findings are consistent with assimilation of transplanted hepatocytes, into host hepatic cords and will facilitate therapeutic applications in metabolic diseases or acute liver failure.