Biomedical Engineering Reference
In-Depth Information
In acute liver failure hepatocyte transplantation may act as a bridge to recovery
and regeneration of the injured native liver or alternatively to orthotopic liver
transplantation once an organ becomes available. The procedure may also be used
in patients who are not candidates for organ transplantation. A major advantage of
hepatocyte transplantation is the immediate availability of cryopreserved cells.
Sufficient cell mass (approximately 10-15 % of liver cell mass) is needed to
provide enough metabolic function [
74
]. The mass of cells, which can be trans-
planted into the liver, is, however, limited. Other options include intrasplenic or
intraperitoneal transplantation, which allow a larger volume of cells. The spleen
has been used successfully as injection site in animals [
75
,
76
] and human
transplantation [
77
]; however, in view of the number of immunologically active
cells located in the spleen, rejection or destruction of the non-native cells needs
consideration. Hepatocyte transplantation in patients with ALF has resulted in a
reduction in ammonia and bilirubin with improvements in hepatic encephalopathy
and cardiovascular instability [
77
,
78
]. In the absence of any randomized con-
trolled trials, it is difficult to comment on the true efficacy of the intervention.
There are a few studies on liver cell therapy for treatment of acute liver failure
in humans with the intention to bridge the patients to orthotopic liver transplan-
tation or recovery. Main challenges for future applications are the appropriate
timing of cell transplantation, the restricted uptake capacity of the recipient liver,
the availability of cells, and the need for immunosuppression to prevent the
rejection of the transplanted cells. The latter point may become more important
than previously considered, since the liver failure gives a high risk for septic
complications itself, which will be aggravated by immunosuppressive drugs.
Extended liver resections have been associated with significant morbidity and
mortality due to hepatic dysfunction or hepatic failure in the postoperative period.
Autologous bone marrow stem cell therapies may offer the potential to enhance
hepatic regeneration in this setting, perhaps increasing the safety of the procedure.
Preclinical models and initial translational studies have suggested that autologous
bone marrow stem cell administration can facilitate hepatic regeneration following
both acute and chronic liver disease [
79
]. Infusion of HSC in three patients after
extended liver resection demonstrated the therapeutic potential, however, more
and controlled clinical trial data are needed [
80
].
10.5.2 Chronic Liver Disease and Liver Fibrosis
Chronic injury and inflammation triggers a gradual loss of liver function and
deposition of extracellular matrix components, which leads to fibrosis and finally
to cirrhosis of the liver. Although acute injury does activate mechanisms of
fibrogenesis, more sustained signals associated with chronic liver diseases lead to a
fibrogenic response which engages several different cell types. Cirrhosis of the
liver as a clinical endpoint of the fibrogenic process is probably an irreversible
condition and the only long-term therapeutic solution for end-stage chronic liver
