Related Experiment Video
Updated: May 10, 2026
Successful Orthotopic Liver Transplantation in Mice Utilizing Microcomputed Tomography Angiography
Published on: September 22, 2023
Serum apolipoprotein E as a marker to monitor graft function after hepatocyte transplantation in a clinically
C Jorns1, T Takahashi, E Callaghan
1Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden. carl.jorns@ki.se
Introduction:
Hepatocyte transplantation, a promising treatment for patients with acute hepatic failure or metabolic liver diseases, requires improvement in engraftment as well as long-term function of the liver cells. We established a hepatocyte transplantation model in apolipoprotein E (ApoE) knockout mice, evaluating serum ApoE and lipoprotein profiles as markers of engraftment of transplanted wild-type hepatocytes. Herein we have described a method to monitor the function of transplanted hepatocytes at low levels of engraftment, corresponding to those reported in clinical cases. We also investigated whether pretreatment with anakinra, an anti-interleukin-1 antagonist, methylprednisolone, or a combination of the two agents improved engraftment.
Methods:
ApoE (-/-) mice were transplanted with hepatocytes isolated from wild-type C57/bl6 mice. A total of 6 × 10(6) hepatocytes were transplanted by 3 separate intrasplenic injections. Animals were treated before transplantation and daily thereafter for 7 days with anakinra, methylprednisolone, or a combination of both. Graft function was monitored by lipoprotein analysis and quantification of ApoE by enzyme-linked immunosorbent assay. Expression of hepatic ApoE mRNA was quantitated by reverse-transcriptase polymerase chain reaction.
Results:
Treatment with anakinra with or without methylprednisolone did not significantly increase serum or hepatic mRNA ApoE expression. The low level of hepatocyte engraftment did not normalize lipoprotein profiles, but produced a significant decline in very low-density lipoprotein and total cholesterol. Repeated transplantations significantly enhanced liver repopulation; serum ApoE levels increased with each infusion, correlating well with hepatic mRNA expression.
Conclusions:
The model of serum ApoE, a sensitive marker of engraftment and transplanted hepatocyte function, allowed us to study hepatocyte transplantation in a clinically relevant manner, that is, without pretreatments such as retrorsine or carbon tetrachloride.
