The authors successfully performed a series of 33 living related liver transplantations (LRLT) on children (15 males and 18 females, ranging from 7 months to 15 years of age) from June 1990 to May 1992, with the informed consent of their parents and the approval of the Ethics Committee of Kyoto University. Before operation, six of the children required intensive care, another 14 were hospitalized, and 13 were homebound. Donors (12 paternal and 21 maternal) were selected solely from the parents of the recipients on the basis of ABO blood group and graft/recipient size matching determined by computed tomography scanning. Procurement of graft was performed using ultrasonic aspirator and bipolar electrocautery without blood vessel clamping and without graft manipulation. All donors subsequently had normal liver function and returned to normal life. The left lateral segment (16 cases), left lobe (16 cases), or right lobe (one case) were used as grafts. The partial liver graft was transplanted into the recipient who underwent total hepatectomy with preservation of the inferior vena cava using a vascular side clamp. Twenty-seven of 33 recipients are alive and well with the original graft and have normal liver function. The patient survival rate was 89% (24/27) in elective cases and 50% (3/6) in emergent cases. The other six recipients had functioning grafts but died of extrahepatic complications. Complications of the graft were minimal in all cases. Hepatic vein stenosis, which occurred three times in two cases, was successfully treated by balloon dilatation. In cases with sclerotic portal vein, the authors anastomosed the portal vein of the graft to the confluence of the splenic vein and the superior mesenteric vein without a vascular graft, after experiencing a case of vascular graft thrombosis. After hepatic artery thrombosis occurred in one of the initial seven recipients whose arterial anastomosis was done with surgical loupe, microsurgery was introduced for hepatic artery reconstruction. There has been no occurrence of thrombosis since then. The current results with LRLT suggested that the meticulous management of surgical factors at each stage of the LRLT procedure is crucial for successful outcome. Living related liver transplantation is a promising option for resolving the graft shortage in pediatric liver transplantation and may be regarded as an independent modality to supplement cadaver donation.

Liver cell transplantation may provide a means to replace lost or deficient liver tissue, but devices capable of delivering hepatocytes to a desirable anatomic location and guiding the development of a new tissue from these cells and the host tissue are needed. We have investigated whether sponges fabricated from poly-L-lactic acid (PLA) infiltrated with polyvinyl alcohol (PVA) would meet these requirements. Highly porous sponges (porosity = 90-95%) were fabricated from PLA using a particulate leaching technique. To enable even and efficient cell seeding, the devices were infiltrated with the hydrophilic polymer polyvinyl alcohol (PVA). This reduced their contact angle with water from 79 to 23 degrees, but did not inhibit the ability of hepatocytes to adhere to the polymer. Porous sponges of PLA infiltrated with PVA readily absorbed aqueous solutions into 98% of their pore volume, and could be evenly seeded with high densities (5 x 10(7) cells/mL) of hepatocytes. Hepatocyte-seeded devices were implanted into the mesentery of laboratory rats, and 6 +/- 2 x 10(5) of the hepatocytes engrafted per sponge. Fibrovascular tissue invaded through the devices' pores, leading to a composite tissue consisting of hepatocytes, blood vessels and fibrous tissue, and the polymer sponge.

Hepatocyte transplantation may provide an alternative to orthotopic liver transplantation to treat liver failure. However, suitable systems to transplant hepatocytes and promote long-term engraftment must be developed. In this study, highly porous, biodegradable sponges were fabricated from poly (L-lactic acid) (PLA), and poly (DL-lacticco-glycolic acid) (PLGA), and utilized to transplant hepatocytes into the mesentery of three groups of Lewis rats. The portal vein was shunted to the inferior vena cava in one group of rats (PCS). The second group of animals received a PCS and a 70% hepatectomy on the day of sponge-hepatocyte implantation (PCS + HEP), and the control group (CON) received no surgical stimulation. The sponges were vascularized by ingrowth of fibrovascular tissue over the first 7 days in vivo. Approximately 95-99% of the implanted hepatocytes (determined utilizing computer-assisted image analysis) died in all three experimental groups during this time. The number of engrafted hepatocytes in the CON group further decreased over the next 7 days to 1.3 +/- 1.1% of the original cell number. However, the number of engrafted hepatocytes in the PCS and PCS + HEP increased over this time to 6 +/- 1% and 5 +/- 2%, respectively. The number of engrafted hepatocytes in the PCS group continued to increase over the next 2.5 months to a value of 26 +/- 12% of the initial cell number, and a large number of engrafted hepatocytes was still present at 6 months. These results indicate that stable new tissues can be engineered by transplanting hepatocytes on biodegradable sponges into heterotopic locations if appropriate stimulation is provided.