Embryonic porcine liver as a source for transplantation: advantage of intact liver implants over isolated hepatoblasts in overcoming homeostatic inhibition by the quiescent host liver.
Cell therapy as an alternative to orthotopic liver transplantation represents a major challenge, since negligible proliferation of isolated hepatocytes occurs after transplantation because of the stringent homeostatic control displayed by the host liver. Thus, different modalities of liver injury as part of the pretransplant conditioning are a prerequisite for this approach. The major objective of the present study was to test whether xenotransplantation of pig fetal liver fragments, in which potential cell-cell and cell-stroma interactions are spared, might afford more robust growth and proliferation compared with isolated pig fetal hepatoblasts. After transplantation into SCID mice, fetal liver tissue fragments exhibited marked growth and proliferation, in the setting of a quiescent host liver, compared with isolated fetal hepatoblasts harvested at the same gestational age (embryonic day 28). The proliferative advantage of fetal pig liver fragments was clearly demonstrated by immunohistochemical and morphometric assays and was observed not only after implantation into the liver but also into extrahepatic sites, such as the spleen and the subrenal capsule. The presence of all types of nonparenchymal liver cells that is crucial for normal liver development and regeneration was demonstrated in the implants. Preservation of the three-dimensional structure in pig fetal liver fragments enables autonomous proliferation of transplanted hepatic cells in the setting of a quiescent host liver, without any requirement for liver injury in the pretransplant conditioning. The marked proliferation and functional maturation exhibited by the pig fetal liver fragments suggests that it could afford a preferable source for transplantation.
Katchman
Helena
H
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Tal
Orna
O
Eventov-Friedman
Smadar
S
Shezen
Elias
E
Aronovich
Anna
A
Tchorsh
Dalit
D
Cohen
Sivan
S
Shtabsky
Alexander
A
Hecht
Gil
G
Dekel
Benjamin
B
Freud
Enrique
E
Reisner
Yair
Y
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation; D004847:Epithelial Cells / Q000166:cytology; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology*; D006706:Homeostasis; D008099:Liver / Q000098:blood supply / Q000166:cytology* / Q000196:embryology*; D016031:Liver Transplantation; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D016513:Mice, SCID; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D013552:Swine; D014183:Transplantation, Heterologous
D012333:RNA, Messenger