| 20025456 |
Dalakas E, Newsome PN, Boyle S, Brown R, Pryde A, McCall S, Hayes PC, Bickmore W, Harrison DJ, Plevris JN: Bone Marrow Stem Cells Contribute to Alcohol Liver Fibrosis in Humans. Stem Cells Dev. 2009 Dec 21.
Bone marrow derived stem cell contribution to liver repair varies considerably and recent evidence suggests these cells may contribute to liver fibrosis. We investigated the mobilization and hepatic recruitment of bone marrow stem cells in patients with alcohol liver injury and their contribution to parenchymal/non-parenchymal liver cell lineages. Liver biopsies from alcoholic hepatitis patients and male patients who received a female liver transplant and developed alcoholic hepatitis, were analyzed for bone marrow stem cell content by FISH and immunostaining. Y-chromosome analysis was performed, along with co-staining for hepatocyte, biliary, myofibroblast and Ki-67 markers. Blood CD34+ levels were quantified in alcoholic hepatitis patients by flow cytometry. Alcoholic hepatitis patients had increased CD34+ cell counts in liver tissue (1.834 +/- 0.605%; p <0.05) and in blood (0.195 +/- 0.063%; p <0.05) as compared with matched controls (0.299 +/- 0.208% & 0.067 +/- 0.01%). A proportion of hepatic myofibroblasts were bone marrow derived (7.9-26.8%) as deemed by the co-localisation of Y chromosome/alpha-SMA staining. In the cross sex liver grafts with alcoholic hepatitis, 5.025% of the myofibroblasts were co-staining for CD34, suggesting that a population of CD34+ cells were contributing to the hepatic myofibroblast population. There was no evidence of bone marrow contribution to hepatocyte or biliary cell differentiation, nor evidence of increased hepatocyte regeneration. Alcohol liver injury mobilizes CD34+ stem cells into the circulation and recruits them into the liver. These bone marrow derived stem cells contribute to the hepatic myofibroblast population but not to parenchymal lineages and do not promote hepatocyte repair. |
1(0,0,0,1) |