Positive effects of cryopreserved adult or fetal liver cell transplants on hypercholesterolemia and hepatic antioxidant defenses in cholesterol-fed rabbits.
The liver plays a central role in lipid metabolism and the pathophysiology of many lipid disorders leads in turn to liver cell injury. Adult hepatocyte transplants provide well-recognized metabolic support, whilst hepatic stem cells may promote liver regeneration and repair, but in both cases, any clinical application would require low temperature banking of the cells. A model of dietary hypercholesterolemia was established in rabbits over 5 months, and transplants of cryopreserved adult hepatocytes (CH) and cryopreserved fetal liver cells (CFLC) were compared to Sham transplants. Cryopreservation was performed by a two-step freezing protocol using 1.5mol/l dimethyl sulfoxide (Me(2)SO). Serum contents of cholesterol lipid classes were measured during the subsequent 4 weeks, in addition to markers of serum and liver oxidative stress. Both CH and CFLC transplantation resulted in a decrease of serum lipids during the 1st week after transplantation. The effect of CH was limited to the 1st week, but CFLC provided a sustained lipid-lowering effect over the 4 weeks. The ultimate outcome of CFLC transplantation by the end of 4 weeks was more pronounced and statistically significant for both serum total cholesterol (0.15+/-0.05 versus 3.65+/-1.4mmol/l) and high-density lipoprotein-cholesterol (0.04+/-0.01 versus 0.56+/-0.06mmol/l) compared to Sham transplants (p<0.05 in both cases). CFLC transplantation also normalized hepatic tissue antioxidant defenses, namely an increase in reduced glutathione content, and enzyme activities for catalase and glutathione reductase (all significantly higher at p<0.05 than in Sham transplants) by 4 weeks.
Lebedinsky
Alexander S
AS
Department of Biochemistry, Institute for Problems of Cryobiology and Cryomedicine, Pereyaslavskaya Street, 23, Kharkov 61015, Ukraine.
Cherkashina
Daria V
DV
Sukach
Alexander N
AN
Volkova
Nataliya A
NA
Fuller
Barry J
BJ
Petrenko
Alexander Yu
AY
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002469:Cell Separation; D015925:Cryopreservation; D016332:Fetal Tissue Transplantation; D022781:Hepatocytes / Q000637:transplantation*; D006937:Hypercholesterolemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015227:Lipid Peroxidation / Q000502:physiology; D008055:Lipids / Q000097:blood; D008099:Liver / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D011817:Rabbits
D000975:Antioxidants; D008055:Lipids