טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentShani Hagit
SubjectImprovement of Transplanted Liver Cell Engraftment and
Function, Cell Detection with PCR for SRY on Y
Choromosome
DepartmentDepartment of Medicine
Supervisor Clinical Professor Yaacov Baruch


Abstract

Background:

Liver cell transplantation is being developed for the treatment of liver failure and inherited metabolic disorders.

Still, this simple procedure is not yet available due to shortage in hepatocytes and low, 5-20%, hepatocyte engraftment efficiency.

The research first aimed to improve the detection of rats' male hepatocytes, following cell transplantation to the spleen, using Y chromosome as a natural marker. Secondly, to improve cell engraftment using VEGF165, an angiogenic factor that encourages hepatocytes survival and proliferation.

Results and discussion:

We have increased detection sensitivity of transplanted cells, using nested PCR, to- 6X102 cells. By semi-quantitative analysis, we estimated liver engraftment, to range between 2X104-2X106.

We have observed the long-term presence of transplanted cells within portal vessels only in the VEGF treated rats. This was in contrast to the common concept, that cells are engrafted to the liver parenchyma via the liver sinusoids, while transplanted cells localized to portal vessels are eliminated within 12-24 hours post transplantation. We therefore suggest a different mechanism by which transplanted cells integrate into the recipient liver: Cells form groups within the portal vessels and translocate into the liver parenchyma directly, or alternatively a new portal vessel is formed, including them within the parenchyma. Our hypothesis explains why transplanted cells are usually seen in groups in portal areas, as reported previously.

The research emphasizes the necessity for early additional interventions in order to establish cell transplantation as a clinical tool for the treatment of liver diseases.