Liver regeneration in a retrorsine/CCl4-induced acute liver failure model: do bone marrow-derived cells contribute?
OBJECTIVE
Adult bone marrow contains progenitors capable of generating hepatocytes. Here a new liver failure model is introduced to assess whether bone marrow-derived progeny contribute to liver regeneration after acute hepatotoxic liver failure.


METHODS
Retrorsine was used to inhibit endogenous hepatocyte proliferation, before inducing acute liver failure by carbon tetrachloride. Bone marrow chimeras were generated before inducing liver failure to trace bone marrow-derived cells. Therefore, CD45 and major histocompatibility complex (MHC) class I dimorphic rat models were applied.


RESULTS
Early after acute liver failure a multilineage inflammatory infiltrate was observed, mainly consisting of granulocytes. In long-term experiments small numbers of CD90+/CD45- cells of donor origin occurred in clusters associated with portal triads. Bone marrow cell infusion was not able to enhance liver regeneration. Cellular hypertrophy was the predominant way of liver mass regeneration in models applying retrorsine.


CONCLUSIONS
Retrorsine pretreatment did not affect sensitivity for carbon tetrachloride. A multilineage inflammatory infiltrate was observed in rats whether pretreated with retrorsine or not. Few donor cells co-expressing CD90 (THY 1) were present in recipient livers, which may resemble donor-derived hematopoietic progenitors or oval cells. No other donor cells within liver parenchyma were detected. This is in contrast to other cell infusion models of acute cell death.
Dahlke
Marc H
MH
Centenary Institute for Cancer Medicine and Cell Biology and Department for Hepatobiliary and Transplantation Surgery, University of Sydney, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney, NSW 2050, Australia. mhdahlke@web.de
Popp
Felix C
FC
Bahlmann
Ferdinand H
FH
Aselmann
Heiko
H
Jäger
Mark D
MD
Neipp
Michael
M
Piso
Pompiliu
P
Klempnauer
Jürgen
J
Schlitt
Hans J
HJ
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002251:Carbon Tetrachloride; D002460:Cell Line / Q000473:pathology; D002678:Chimera; D004195:Disease Models, Animal; D006098:Granulocytes / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D008115:Liver Regeneration; D011763:Pyrrolizidine Alkaloids; D051381:Rats; D011917:Rats, Inbred Lew; D018800:Thy-1 Antigens / Q000378:metabolism
D011763:Pyrrolizidine Alkaloids; D018800:Thy-1 Antigens; D002251:Carbon Tetrachloride; D017493:Leukocyte Common Antigens; C003300:retrorsine