HEPATOCELLULAR TRANSPLANTATION AND TARGETING GENETIC MARKERS TO HEPATIC CELLS 
PROPOSED HUMAN EXPERIMENTS (calculated/kg') 
cells 2.00E+08 2.00E+08 4.17E+09/kg 
% cells 4.80% 4.80% 
HUMAN DATA EXTRAPOLATED FOR "IDEAL" 70kg INDIVIDUAL 
(maximum estimate of number of liver cells - 10‘^) 
cells 1.40E+10 1.40E+10 70 l.OOE+12 
% cells 1.40% 1.40% 
50% survival 0.70% 0.70% 
(number of liver cells extrapolated from murine experiments) 
cells 1.40E+10 1.40E+10 70 2.92E+11 
% cells 4.80% 4.80% 
50% survival 2.40% 2.40% 
(minimum estimate of number of liver cells - 10") 
cells 1.40E+10 1.40E+10 70 l.OOE+11 
% cells 14.00% 14.00% 
50% survival 7 . 00% 7 . 00% 
It is difficult to predict quantitatively the effect of the patient's underlying 
liver disease on the ratio of donor to host hepatocytes (or total hepatic cells) . The 
patient's underlying hepatic disease will presumably reduce the number of healthy 
hepatic cells and may potentially improve the fraction of cells in the recipient which 
will be derived from the donor. Inflammation of the recipient's liver might have an 
opposite effect (particularly for DNA analysis) by introducing large numbers of 
inflammatory cells (lymphocytes.) Of potential importance also is the fact that the 
underlying hepatic disease in many of these patients will effectively produce 
hepatectomy similar to that seen in animals with experimentally induced (chemical) 
hepatectomy which creates conditions favorable for hepatocellular proliferation. It is 
possible that the normal transplanted cells will respond to these conditions and the 
number of cells derived from the transplant may increase at least 2-4 fold. In 
metabolic diseases there is no reason to expect such quantitative benefit. 
C. Surgical approaches to the delivery of hepatocytes. 
The principle goal of this protocol is to investigate methods for transplanting 
hepatocytes into human subjects. As described above, two methods which have been 
employed successfully in animal experiments are infusion into the portal vein and 
intrasplenic injection. While intrasplenic injection has been the preferred procedure 
in animal studies, we believe that methods for HCT without laparotomy would improve 
the risk/benefit ratio and the efficacy of HCT relative to OLT in general. Several 
methods for introducing catheters into the portal vein are possible including open 
catheterization with laparotomy, catheterization by laparoscopy, direct transhepatic 
catheterization, and trans jugular catheterization. There are different indications and 
complications for each of these procedures. The disadvantage of using the portal venous 
system is the risk of portal vein thrombosis. It is also theoretically possible to 
introduce hepatocytes to the liver via the arterial system (hepatic artery or splenic^ 
[808] 
Recombinant DNA Research, Volume 14 
