title: Hepatocyte transplantation into diseased mouse liver. Kinetics of parenchymal repopulation and identification of the proliferative capacity of tetraploid and octaploid hepatocytes.
abstract: To examine the process of liver repopulation by transplanted hepatocytes, we developed transgenic mice carrying a mouse major urinary protein-urokinase-type plasminogen activator fusion transgene. Expression of this transgene induced diffuse hepatocellular damage beginning at 3 weeks of age, and homozygous mice supported up to 97% parenchymal repopulation by healthy donor hepatocytes transplanted into the spleen. Using this transplantation model, we determined that 1) a mean of 21% of splenically injected hepatocytes engraft in liver parenchyma; 2) a mean of 6.6% of splenically injected hepatocytes (or one-third of engrafted cells) can give rise to proliferating hepatocyte foci; 3) transplanted cells in proliferating foci display an initial cell-doubling time of 28 hours, and focus growth continues through a mean of 12 cell doublings; 4) hepatocytes isolated from young and aged adult mice display similar focus repopulation kinetics; 5) the extent of repopulated parenchyma remains stable throughout the life of the recipient mouse; and 6) tetraploid and octaploid hepatocytes can support clonal proliferation.
authors: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors: T C
authors: TC
authors: Weglarz
authors: J L
authors: JL
authors: Degen
authors: E P
authors: EP
authors: Sandgren
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D002455:Cell Division; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D007267:Injections; D007700:Kinetics; D008107:Liver Diseases / Q000601:surgery*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D011003:Ploidies; D011506:Proteins / Q000235:genetics; D013154:Spleen; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics
chemical_list: D011506:Proteins; C035737:major urinary proteins; D014568:Urokinase-Type Plasminogen Activator