Liver repopulation trial using bone marrow cells in a retrorsine-induced chronic hepatocellular injury model.
OBJECTIVE
The aim of this study was to determine the potential of bone marrow derived cells to participate in liver repopulation. In this model, the injected cells had a "selective growth advantage" compared to the native hepatocytes whose proliferation was blocked by retrorsine.


METHODS
Total bone marrow cells were isolated from male Fisher 344 rats not deficient in dipeptidyl peptidase activity (F344, DPP IV+). The animals were given an injection of retrorsine and were divided in 2 groups: 1/group R (N=13): female F344 rats received 4.106 male cells at day 0 (labeled by chromosome Y). 2/group RH (N=19): Male F344 DPP IV- rats received 4.106 male DPP IV+ cells after hepatectomy at day 0 (labelled by DPP IV activity).


RESULTS
Group R: no male cell was detected by PCR at day 14, 28, 56 and 84. Group RH: isolated DPP IV+ transplanted cells were observed at days 14 and 28 in the periportal areas. Later, these cells were no longer visible. Liver regeneration occurred by proliferation of small clusters of hepatocytes.


CONCLUSIONS
In this experimental model the capacity of transplanted bone marrow cells to repopulate the liver was tested against the same capacity of native liver stem cells. Liver regeneration occurred via native liver cells seen as small hepatocytes. In this model the small hepatocytes may be considered as hepatic stem cells.
Kohneh-Shahri
Niaz
N
Laboratoire des Thérapeutiques Innovantes des Maladies du Foie (EA 1833), Université René Descartes Paris V.
Regimbeau
Jean-Marc
JM
Terris
Benoît
B
Paradis
Valérie
V
Bralet
Marie-Pierre
MP
Coleman
William
W
Butz
Genelle
G
Chouzenoux
Sandrine
S
Houssin
Didier
D
Soubrane
Olivier
O
D000818:Animals; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D056486:Chemical and Drug Induced Liver Injury; D002908:Chronic Disease; D005260:Female; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D008107:Liver Diseases / Q000601:surgery*; D008115:Liver Regeneration; D008297:Male; D011763:Pyrrolizidine Alkaloids / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D011763:Pyrrolizidine Alkaloids; C003300:retrorsine