Hepatic Differentiation of Bone Marrow Derived Mesenchymal Stem Cell Using Fibrin Gels in 70% Hepatectomized Rat

ABSTRACT

PURPOSE: To investigate the differentiation of rat bone marrow-derived mesenchymal stem cells (MSCs) into hepatocytes by cell transplantation using fibrin gels in a 70% hepatectomized rat model. METHODS: MSCs were isolated from Sprague-Dawley rats. MSCs (1.5x10(7) cells) were mixed with fibrin gels and injected immediately into the abdominal cavity of 70% hepatectomized rats. Fibrin-gels consisted of 500 IU/ml of thrombin and 90 mg/ml of fibrinogen. Transplanted MSCs in the fibrin scaffold were retrieved from surgically opened peritoneal cavities of rats on days 5, 10, 15, and 21 after the operation. The specimens were analyzed histologically and immunohistochemically. RESULTS: On H&E staining, MSCs from hepatectomized rats had changed to a round shape, while MSCs of the control group kept their spindle shape. When the fibrin matrix was biodegraded at day 15, the morphology of the MSCs had changed to hepatocyte-like cells without sinusoids and the hepatocyte-like cells had formed a three-dimensional tissue permitting cell-to-cell contacts within the matrix. On immunohistochemistry, MSCs expressed the hepatocyte markers cytokeratin 18, albumin, and alpha-fetoprotein, after 15 days of transplantation. CONCLUSION: When bone marrow-derived MSCs are transplanted using fibrin gels in the 70% hepatectomized rat, MSCs differentiate into hepatocyte-like cells and are conglomerated so that they form three-dimensional tissue-like hepatocytes without sinusoids.