A novel approach for introducing hepatocytes into the portal circulation

Many attempts have been made to treat metabolic diseases of the liver. One approach, called ex vivo gene therapy, is based on correcting the genetic defect in the patient's hepatocytes. In this model, the liver is resected and hepatocytes are isolated, plated in culture, and genetically corrected with recombinant retroviruses. The cells are then harvested and infused into the portal circulation, where they seed in the sinusoids of the liver. In this study, a canine model was used to develop an approach to ex vivo gene therapy that requires only one surgical procedure. The basic concept is to place a catheter in the mesenteric circulation at the time of liver resection that can be used subsequently to deliver hepatocytes into the liver. With four 18 to 28 kg mongrel dogs, a laparotomy was performed, the left lateral segment of the liver was resected, and a 9.5 Fr Hickman catheter was introduced into the inferior mesenteric vein. At 10 days, the catheter was studied angiographically and removed. The catheter remained patent and was easily removed without untoward effects. A subsequent necropsy was performed to evaluate the consequences of this procedure. There was no hematoma at the site of the catheter placement or evidence for intraportal clot. This approach has been used in subsequent studies to treat a patient with familial hypercholesterolemia.