Autologous bone marrow cell infusion therapy for liver cirrhosis.
The plasticity of bone marrow cells (BMC) has been confirmed by autopsy results of female recipients of BMC from male donors. To establish new clinical therapies for patients with liver cirrhosis using autologous BMC, we developed a new in vivo murine model using green fluorescent protein (GFP) and repeated carbon tetrachloride (CCl(4)) injection. We found that BMC infused through the tail vein, efficiently repopulated cirrhotic liver tissue and, under the influence of persistent liver damage induced by carbon tetrachloride, differentiated into albumin-producing hepatocytes. Moreover, such BMC infusions into mice with cirrhosis improved liver function and reduced mortality. The latter observation correlated with the strong expression of matrix metalloproteinases (MMP), particularly MMP-9, and reduced hepatic fibrosis. The results from the 'GFP/CCl(4) model' showed that cell therapy using autologous BMC has the potential to become an effective treatment for patients with liver failure due to advanced liver cirrhosis. This review summarizes previous findings plus these recent experimental results, as well as recent clinical trials of BMC transfusion into patients with end-stage chronic liver disease.
Sakaida
Isao
I
Department of Gastroenterology and Hepatology, Yamaguchi University, Graduate School of Medicine, Ube, Yamaguchi Prefecture, Japan. sakaida@yamaguchi-u.ac.jp
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002251:Carbon Tetrachloride; D002454:Cell Differentiation; D049109:Cell Proliferation; D002986:Clinical Trials as Topic; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008115:Liver Regeneration; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D000418:Albumins; D049452:Green Fluorescent Proteins; D002251:Carbon Tetrachloride; D020782:Matrix Metalloproteinases