title: HVEGF165 increases survival of transplanted hepatocytes within portal radicles: suggested mechanism for early cell engraftment.
abstract: VEGF is a potent angiogenic factor that promotes hepatocyte growth, increases permeability of blood vessels, and induces vasodilatation, and may accelerate engraftment and function of transplanted hepatocytes. The aim was to study the effect of VEGF on early hepatocyte engraftment. Thirty-two Lewis syngeneic female rats underwent 70% partial hepatectomy. Eighteen received 240 ng VEGF165 and 14 received saline for control. Thereafter, intrasplenic transplantation of 10(7) male hepatocytes was done. Semiquantitative analysis of PCR product of the SRY region of the Y-chromosome was performed. Paraffin-embedded sections were stained for H&E and for PCNA immunostaining. By PCR, male hepatocytes were identified in 8 livers out of 14 VEGF-treated rats at 24-48 h, compared with only 1 liver out of 8 controls. Transplanted cells were seen within portal vessels radicles in 7 out of 14 VEGF-treated rats for as long as 48 h posttransplantation, compared with only one control liver at 24 h. There was no histological sign of cell injury to transplanted or adjacent cells. Two weeks after transplantation male transplanted cells were identified in two out of four rats treated with hVEGF165 and in one out of six rats treated with saline. No transplanted cells were detected within portal tracts 14 days after transplantation. hVEGF165 enhances the presence of transplanted hepatocytes within portal vessels after transplantation. We suggest an additional mechanism for cell engraftment, whereby transplanted hepatocytes first stick to each other in the portal radicles. Later they become included in the liver parenchyma as groups of organized cells in a process stimulated by VEGF.
authors.affiliation: Liver Unit, Rambam Medical Center, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 31096 Haifa, Israel.
authors.forename: Hagit
authors.initials: H
authors.lastname: Shani-Peretz
authors.forename: Vladislav
authors.initials: V
authors.lastname: Tsiperson
authors.forename: Gideon
authors.initials: G
authors.lastname: Shoshani
authors.forename: Ella
authors.initials: E
authors.lastname: Veitzman
authors.forename: Gera
authors.initials: G
authors.lastname: Neufeld
authors.forename: Yaacov
authors.initials: Y
authors.lastname: Baruch
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D017690:Cell Transplantation; D004247:DNA / Q000032:analysis / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects* / Q000637:transplantation; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D016133:Polymerase Chain Reaction; D011169:Portal Vein / Q000166:cytology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012709:Serum Albumin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D043925:Angiogenesis Inducing Agents; D018809:Proliferating Cell Nuclear Antigen; D012709:Serum Albumin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004247:DNA; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D001663:Bilirubin