Status and Prospects of Liver Cirrhosis Treatment by Using Bone Marrow-Derived Cells and Mesenchymal Cells

• Published in: Tissue engineering. Part B, Reviews Reviews, 2014-06, Vol.20 (3), p.26-210
• Main Authors: Terai, Shuji, Takami, Taro, Yamamoto, Naoki, Fujisawa, Koichi, Ishikawa, Tsuyoshi, Urata, Yohei, Tanimoto, Haruko, Iwamoto, Takuya, Mizunaga, Yuko, Matsuda, Takashi, Oono, Takashi, Marumoto, Miho, Burganova, Guzel, Fernando Quintanilha, Luiz, Hidaka, Isao, Marumoto, Yoshio, Saeki, Issei, Uchida, Koichi, Yamasaki, Takahiro, Tani, Kenji, Taura, Yasuho, Fujii, Yasuhiko, Nishina, Hiroshi, Okita, Kiwamu, Sakaida, Isao
• Format: Article
• Language: English
• Subjects: Animals; Bone marrow; Bone Marrow Cells - pathology; Bone Marrow Transplantation - trends; Cell Differentiation; Drug therapy; Forecasting; Hepatitis B virus; Hepatitis C virus; Human immunodeficiency virus; Humans; Liver cirrhosis; Liver Cirrhosis - pathology; Liver Cirrhosis - therapy; Liver Regeneration - physiology; Mesenchymal Stem Cell Transplantation - trends; Mesenchymal Stromal Cells - pathology; Special Focus; Stem cells; Tissue Engineering - trends
• ISSN: 1937-3368; 1937-3376
• DOI: 10.1089/ten.teb.2013.0527

In 2003, we started autologous bone marrow cell infusion (ABM i ) therapy for treating liver cirrhosis. ABM i therapy uses 400 mL of autologous bone marrow obtained under general anesthesia and infused mononuclear cells from the peripheral vein. The clinical study expanded and we treated liver cirrhosis induced by HCV and HBV infection and alcohol consumption. We found that the ABM i therapy was effective for cirrhosis patients and now we are treating patients with combined HIV and HCV infection and with metabolic syndrome-induced liver cirrhosis. Currently, to substantiate our findings that liver cirrhosis can be successfully treated by the ABM i therapy, we are conducting randomized multicenter clinical studies designated “Advanced medical technology B” for HCV-related liver cirrhosis in Japan. On the basis of our clinical study, we developed a proof-of-concept showing that infusion of bone marrow cells (BMCs) improved liver fibrosis and sequentially activated proliferation of hepatic progenitor cells and hepatocytes, further promoting restoration of liver functions. To treat patients with severe forms of liver cirrhosis, we continued translational research to develop less invasive therapies by using mesenchymal stem cells derived from bone marrow. We obtained a small quantity of BMCs under local anesthesia and expanded them into mesenchymal stem cells that will then be used for treating cirrhosis. In this review, we present our strategy to apply the results of our laboratory research to clinical studies.