In Vitro and In Vivo Evaluation of Albumin Synthesis Rate of Porcine Hepatocytes in a Flat-Plate Bioreactor

Authors

  • Masaya Shito,

    1. Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Shriners Hospitals for Children, and Harvard Medical School, Boston, Massachusetts, U.S.A.
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  • Nam Heui Kim,

    1. Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Shriners Hospitals for Children, and Harvard Medical School, Boston, Massachusetts, U.S.A.
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  • Harihara Baskaran,

    1. Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Shriners Hospitals for Children, and Harvard Medical School, Boston, Massachusetts, U.S.A.
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  • Arno W. Tilles,

    1. Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Shriners Hospitals for Children, and Harvard Medical School, Boston, Massachusetts, U.S.A.
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  • Ronald G. Tompkins,

    1. Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Shriners Hospitals for Children, and Harvard Medical School, Boston, Massachusetts, U.S.A.
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  • Martin L. Yarmush,

    1. Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Shriners Hospitals for Children, and Harvard Medical School, Boston, Massachusetts, U.S.A.
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  • Mehmet Toner

    1. Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Shriners Hospitals for Children, and Harvard Medical School, Boston, Massachusetts, U.S.A.
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  • The first two authors contributed equally to this paper.

Address correspondence and reprint requests to Dr. Mehmet Toner, Center for Engineering in Medicine, Massachusetts General Hospital, Bigelow 1401, 55 Fruit Street, Boston, MA 02114, U.S.A. E-mail: mtoner@sbi.org

Abstract

Abstract: Several configurations of extracorporeal bioartificial liver devices have been developed for the potential treatment of fulminant hepatic failure or as a bridge to liver transplantation. Recently, we developed a microchannel flat-plate bioreactor with an internal membrane oxygenator in which porcine hepatocytes are cultured as a monolayer on the bottom glass surface. In the present study, we investigated synthetic function of porcine hepatocytes in the bioreactor in both in vitro and in vivo flow circuit models. In vitro, albumin synthesis was stable in the bioreactor for up to 4 days of perfusion. In vivo, with the extracorporeal connection of the bioreactor to rat vasculature, porcine albumin was detectable for 24 h in the rat plasma. We also developed a simple mathematical model to predict the in vivo porcine albumin concentration in rat plasma. These results indicate that this configuration of a microchannel flat-plate bioreactor has potential as a liver support device and warrants further investigation.

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