Artificial cells in liver disease - Artificial Cells, Cell Engineering and Therapy - page 225

for up to 6±8 weeks post-transplantation. Thereafter, the membrane surrounding
the microcapsule deteriorates, causing physical breakdown of the micro-
capsule. 24 It has been speculated that degeneration of the microencapsulated
hepatocytes (autolysis) leads to ionic and pH changes within the microcapsule
microenvironment. 24 These pH changes may weaken the alginate±polylysine co-
polymer membrane of the microcapsule by altering the charges on the molecules
that constitute the membrane. Thus, degenerative changes observed in the
microcapsules beginning at 2 months post-transplantation suggest that repeated
transplantation may be necessary for long-term effectiveness of micro-
encapsulated hepatocytes. 16 In a subsequent 6 month study, repeated monthly
transplantation of microencapsulated hepatocytes in Gunn rats demonstrated a
prolonged and sustained decrease in serum bilirubin levels. 16 Repeated monthly
transplantation of microencapsulated hepatocytes, performed before the pre-
vious month's microencapsulated hepatocyte transplant began to deteriorate,
provided sustained reduction in hyperbilirubinemia. In contrast, the control rats
that received empty microcapsules experienced no reduction in hyper-
bilirubinemia.
For microencapsulated hepatocyte transplantation to provide a viable form of
artificial liver support (e.g. bridge-to-transplantation), it must be simple and
convenient to use. Large quantities of healthy microencapsulated hepatocytes
must be readily available for transplantation when required. In concept, a facility
akin to a blood bank in which microencapsulated hepatocytes could be stored
and used as needed would be ideal. Cryopreservation is a standard procedure for
preserving various cell types and can effectively be used to store micro-
encapsulated hepatocytes. It has been demonstrated that cryopreserved,
microencapsulated hepatocytes functioned as well as freshly prepared, non-
frozen microencapsulated hepatocytes both in vitro and in vivo. 26 Thus,
transplantation of cryopreserved microencapsulated hepatocytes can provide a
convenient therapeutic option for the management of fulminant hepatic failure
as well as of inborn errors of metabolism without need for immunosuppression.
Despite encouraging studies with microencapsulated and microcarrier
attached hepatocytes, it now appears that such techniques may be useful only
for providing temporary liver support. The limited lifespan of primary
hepatocyte culture requires multiple transplantations of microcarrier or
microencapsulated hepatocytes, and may not be ideally suited for the clinical
setting. The accumulation of microcarriers and breakdown products of micro-
capsules may present a safety concern not be suitable for patients with severe
liver disease. Thus, attention has again focused on transplanting hepatocytes
directly in the liver via the intraportal route. Recent clinical studies have also
demonstrated that the previous fears of portal vein obstruction by transplanted
hepatocytes are not justified, provided a slow controlled infusion of hepatocytes
can be accomplished.