| セッション情報 | The 8th JSGE-AGA Joint Meeting |
|---|---|
| タイトル | JM-4：Development of New Cell Therapy for Liver Fibrosis |
| 演者 | Terai Shuji（Department of Gastroenterology ＆ Hepatology, Yamaguchi University Graduate School of Medicine, Japan） |
| 共同演者 | Takami Taro（Department of Gastroenterology ＆ Hepatology, Yamaguchi University Graduate School of Medicine, Japan）, Sakaida Isao（Department of Gastroenterology ＆ Hepatology, Yamaguchi University Graduate School of Medicine, Japan） |
| 抄録 | Liver cirrhosis patients generally progress to liver failure. To cure this progressive disease, we developed a novel cell therapy using bone marrow cells；autologous bone marrow cell infusion（ABMi）therapy（Stem Cells 2006）. The mechanism of cell therapy is that bone marrow cell infusion improved liver fibrosis and sequentially activated hepatocyte proliferation and liver progenitor cell. These effect improved liver function and survival rate. Previous clinical studies of ABMi therapy also showed safety and effective for liver cirrhosis patient. In human hepatocyte proliferation and activation of liver progenitor cell after autologous bone marrow cell infusion was also found. Now we prepared a new randomized clinical trial to evaluate the effects of ABMi therapy. However, ABMi therapy may not be possible in patients who are unable to undergo general anesthesia；therefore, we have started to develop a next-generation stem cell therapy using cultured cells from bone marrow. We made cirrhosis model mice by repeatedly administering carbon tetrachloride to NOD-SCID mice for 6 weeks. Human bone marrow mononuclear cells（Lonza, 2M-125A）were seeded in culture flasks and cultured in 10% FBS-DMEM. Cultured BMC was differentiated into Mesechymal stem cell during 20 days. We cultured bone marrow cells by two system, one system is no passage system（P0）and other system is two passage system（P2）during 20 culture day. P0 cell consisted with 66.2±11.7% Mesenchymal stem cells（MSC：CD73/CD90/CD105 positive and CD45 negative）and with 16.5±13.9% Macrophage（CD45/CD11b）. P2 cell consisted with 94.1±2.6 MSC and 0.25±0.14% is macrophage. During 20 days the number of cells increased 43-fold. We also confirmed multiple cell lineage of this MSC. Cultures P0 cells and P2 cells infusion significantly inhibited liver fibrosis（p＜0.05）in LC NOD-SCID mice. Compared with improvement of liver fibrosis, P2 cell infusion was more significantly improved liver fibrosis（p＜0.05）. Concerning with cell fraction, purified MSC with deletion macrophage infusion was significantly improved liver fibrosis than that in cell fraction contaminating macrophages. Depend on the results of these basic study, we proceeded safety evaluation of MSC using dog system. In this seminar, we will present current status and future perspective of cell therapy for liver fibrosis. |
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