title: Bone-marrow-derived cells cultured in serum-free medium reduce liver fibrosis and improve liver function in carbon-tetrachloride-treated cirrhotic mice.
abstract: We have previously developed autologous bone marrow cell infusion (ABMi) therapy for liver cirrhosis patients. One problem associated with ABMi therapy is that general anesthesia is required to obtain 400 ml bone marrow fluid from liver cirrhosis patients. However, many patients with decompensated cirrhosis do not meet the criteria, because of decreased liver function or an increased bleeding tendency. To overcome these issues, our aim is to derive liver repair cells from small amounts of autologous bone marrow aspirates obtained under local anesthesia and to use these cells in liver cirrhosis patients. Here, we conducted, by using a mouse model, basic research aimed at achieving novel liver regeneration therapy. We cultured bone marrow cells aspirated from the femurs of C57 BL/6 Tg14 (act-EGFP) OsbY01 mice (green fluoresent protein [GFP]-transgenic mice). After 14 days of culture with serum-free medium (good manufacturing practice grade), the obtained spindle-shaped GFP-positive cells were injected (1×10(4) cells) via the caudal vein into mice with carbon tetrachloride (CCl4)-induced cirrhosis. Numerous cultured macrophages and some mesenchymal stem cells repopulated the cirrhotic liver. The results showed that serum albumin, liver fibrosis and liver function were significantly improved in the group treated with cultured bone marrow cells (P<0.01). Moreover, matrix metalloproteinase-9 expression was increased in the liver (P<0.01). Thus, infusion of bone-marrow-derived cultured cells improved liver function and liver fibrosis in mice with CCl4-induced cirrhosis.
authors.affiliation: Department of Gastroenterology & Hepatology, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi, 755-8505, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Shuji
authors.initials: S
authors.lastname: Terai
authors.forename: Takuro
authors.initials: T
authors.lastname: Hisanaga
authors.forename: Taro
authors.initials: T
authors.lastname: Takami
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Shoko
authors.initials: S
authors.lastname: Watanabe
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D002251:Carbon Tetrachloride; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control / Q000628:therapy*; D008111:Liver Function Tests; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D016895:Culture Media, Serum-Free; D012709:Serum Albumin; D049452:Green Fluorescent Proteins; D002251:Carbon Tetrachloride; D020780:Matrix Metalloproteinase 9