Therapeutic liver reconstitution with murine cells isolated long after death.
OBJECTIVE
Due to the shortage of donor organs, many patients needing liver transplantation cannot receive one. For some liver diseases, hepatocyte transplantation could be a viable alternative, but donor cells currently are procured from the same sources as whole organs, and thus the supply is severely limited.


METHODS
Here, we investigated the possibility of isolating viable hepatocytes for liver cell therapy from the plentiful source of morgue cadavers. To determine the utility of this approach, cells were isolated from the livers of non-heart-beating cadaveric mice long after death and transplanted into fumarylacetoacetate hydrolase-deficient mice, a model for the human metabolic liver disease hereditary tyrosinemia type I and a stringent in vivo model for hepatic cell transplantation.


RESULTS
Surprisingly, complete and therapeutic liver repopulation could be achieved with hepatocytes derived up to 27 hours post mortem.


CONCLUSIONS
Competitive repopulation experiments showed that cadaveric liver cells had a repopulation capacity similar to freshly isolated hepatocytes. Importantly, viable hepatocytes also could be isolated from cadaveric primate liver (monkey and human) efficiently. These data provide evidence that non-heart-beating donors could be a suitable source of hepatocytes for much longer time periods than previously thought possible.
Erker
Laura
L
Oregon Stem Cell Center, Oregon Health and Science University, Portland, Oregon 97239, USA. erkerl@ohsu.edu
Azuma
Hisaya
H
Lee
Andrew Y
AY
Guo
Changsheng
C
Orloff
Susan
S
Eaton
Laura
L
Benedetti
Eric
E
Jensen
Bryan
B
Finegold
Milton
M
Willenbring
Holger
H
Grompe
Markus
M
D000818:Animals; D015415:Biomarkers / Q000097:blood; D002102:Cadaver; D049109:Cell Proliferation; D002469:Cell Separation; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000201:enzymology / Q000637:transplantation*; D006801:Humans; D006867:Hydrolases / Q000172:deficiency* / Q000235:genetics; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008115:Liver Regeneration; D008253:Macaca mulatta; D051379:Mice; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics; D022661:RNA, Untranslated; D013696:Temperature; D013997:Time Factors; D014443:Tyrosine / Q000097:blood; D020176:Tyrosinemias / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000601:surgery*
D015415:Biomarkers; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D011506:Proteins; D022661:RNA, Untranslated; D014443:Tyrosine; D006867:Hydrolases; C020156:fumarylacetoacetase