Little evidence of bone marrow-derived hepatocytes in the replacement of injured liver.
We have tested the ability of bone marrow (BM) cells (BMCs) to form hepatocytes in liver injury models. We used three models: (i) carbon tetrachloride (CCl4) treatment, (ii) albumin-urokinase transgenic mouse [TgN(Alb1Plau)], and (iii) hepatitis B transgenic mouse [TgN(Alb1HBV)]. As a nonselective liver injury model, irradiated C57BL/6 (B6) mice were transplanted with BMCs from GFP transgenic mouse [TgN(ActbEGFP)] or beta-galactosidase transgenic mouse [TgN(MtnLacZ)] followed by the administration of CCl4. Irradiated TgN(Alb1HBV) and TgN(Alb1Plau) were also transplanted with BMCs from TgN(ActbEGFP) or TgN(MtnLacZ). Approximately 1.5 x 106 hepatocytes per liver were analyzed for GFP-positive cells, and the whole livers were inspected for beta-galactosidase expression. No GFP-positive hepatocytes and no gross blue staining of the livers with 5-bromo-4-chloro-3-indolyl beta-d-galactoside in any of the 18 recipient mice analyzed were detected. The livers from female animals with gender-mismatched BM transplantation were also tested with Y chromosome fluorescent in situ hybridization analysis to detect donor-derived cells. A total of five isolated hepatocytes were positive for Y chromosome in 4.1 x 105 hepatocytes analyzed. Our results demonstrate that there is little or no contribution of BMCs to the replacement of injured livers in these models. We conclude that BM-derived cells cannot generally lead to a cure of liver damage.
Kanazawa
Yoshiyuki
Y
Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037, USA.
Verma
Inder M
IM
D000818:Animals; D000831:Animals, Newborn; D016026:Bone Marrow Transplantation / Q000473:pathology*; D002251:Carbon Tetrachloride / Q000633:toxicity; D049452:Green Fluorescent Proteins; D006514:Hepatitis B Surface Antigens / Q000235:genetics; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation*; D008099:Liver / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D006514:Hepatitis B Surface Antigens; D008164:Luminescent Proteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D002251:Carbon Tetrachloride