Observations on initial cell loss after intraportal hepatocyte transplantation of 5'-bromo-deoxy-uridine-labeled hepatocytes.
In the present study, attempts are made to improve posttransplant survival of intraportally transplanted hepatocytes in a syngeneic hepatocyte transplantation (HTX) model. Engrafted hepatocytes were detected and quantified after pretransplant labeling with 5'-bromo-deoxy-uridine. In order to enhance the survival percentage, three mechanisms that possibly influence cell survival were manipulated: (1) administration of Matrigel (extracellular-matrix components, Matrigel Basement Membrane Complex, Micronic BV, Lelystad, The Netherlands) in order to improve the environmental conditions of the transplanted hepatocytes; (2) immunosuppression of the recipients by 5 Gy total body irradiation and cyclosporin-A administration (25 mg/kg, 3 x weekly), and (3) Kupffer cell depletion by injection of dichloromethylene-diphosphonate-filled liposomes. The results were analyzed in relation to HTX without treatment. Cell survival was approximately 14% (10 days after HTX), and the transplanted hepatocytes were distributed equally throughout the various recipient liver lobes. However, no increase was attained by Matrigel coadministration, immunosuppression, or Kupffer cell depletion.
Kocken
J M
JM
Department of Surgery, Leiden University Medical Center, The Netherlands.
Bouwman
E
E
Borel Rinkes
I H
IH
Sinaasappel
M
M
Terpstra
O T
OT
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival; D004002:Clodronic Acid / Q000008:administration & dosage; D003094:Collagen; D004338:Drug Combinations; D006085:Graft Survival; D007165:Immunosuppression Therapy; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology; D007797:Laminin; D008081:Liposomes; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016031:Liver Transplantation / Q000379:methods / Q000473:pathology*; D008297:Male; D011509:Proteoglycans; D051381:Rats; D011917:Rats, Inbred Lew; D014185:Transplantation, Isogeneic
D004338:Drug Combinations; D007797:Laminin; D008081:Liposomes; D011509:Proteoglycans; D004002:Clodronic Acid; C059485:matrigel; D003094:Collagen; D001973:Bromodeoxyuridine