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

70% 간절제술을 받은 쥐에서 피브린젤을 이용한 중간엽줄기세포의 생체내 간세포 분화

  • Shin, Woo-Young (Department of Surgery, Chonnam National University College of Medicine) ;
  • Jung, Sung-Eun (Department of Surgery, Seoul National University College of Medicine) ;
  • Min, Hye-Sook (Department of Pathology, Seoul National University College of Medicine) ;
  • Lee, Hae-Won (Department of Surgery, Seoul National University College of Medicine) ;
  • Cho, Eung-Ho (Department of Surgery, Seoul National University College of Medicine) ;
  • Yi, Nam-Joon (Department of Surgery, Seoul National University College of Medicine) ;
  • Suh, Kyung-Suk (Department of Surgery, Seoul National University College of Medicine) ;
  • Lee, Kuhn-Uk (Department of Surgery, Seoul National University College of Medicine)
  • 신우영 (전남대학교 의과대학 외과학교실) ;
  • 정성은 (서울대학교 의과대학 외과학교실) ;
  • 민혜숙 (서울대학교 의과대학 병리학교실) ;
  • 이해원 (서울대학교 의과대학 외과학교실) ;
  • 조응호 (서울대학교 의과대학 외과학교실) ;
  • 이남준 (서울대학교 의과대학 외과학교실) ;
  • 서경석 (서울대학교 의과대학 외과학교실) ;
  • 이건욱 (서울대학교 의과대학 외과학교실)
  • Published : 2010.06.30

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 ($1.5{\times}10^{7}$ 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.

Keywords

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