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The Liver is Super Super Awesome

The Liver is Super Super Awesome. Olga Filippova, Munir Nahri, Akash Patel BMES 471. Anatomy of the Liver 1. Most metabolically complex organ 2 main, 2 smaller lobe Eight segments Lobules Dual blood supply Portal vein (75%) Hepatic artery (25%) Sinusoidal hepatocyte plates

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The Liver is Super Super Awesome

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  1. The Liver is Super Super Awesome Olga Filippova, Munir Nahri, Akash Patel BMES 471

  2. Anatomy of the Liver1 • Most metabolically complex organ • 2 main, 2 smaller lobe • Eight segments • Lobules • Dual blood supply • Portal vein (75%) • Hepatic artery (25%) • Sinusoidal hepatocyte plates • Endothelial, Kupffer’s, Fat-storing, Pit http://education.vetmed.vt.edu/curriculum/vm8054/labs/Lab20/LAB20.HTM http://www.chinaphar.com/1671-4083/24/figs/4747f2.jpg http://www.cpmc.org/images/liver/topics/liver_segments.jpg

  3. Functions of the Liver1 • Metabolism • Glucose regulation • Amino acid catabolism • Drug neutralization • Bile synthesis • Digestion of fat • Cholesterol catabolism • Stored in gallbladder • Released by CCK from SI http://www.genesishealth.com/services/bariatric_surgery/digestive_diagram.aspx

  4. Current State of Liver TE2 • Pgusighisghsdg Abu-Absi et al.3 Du et al.4

  5. Current State of Liver TE2 • Pgusighisghsdg http://www.oulu.fi/spareparts/ebook_topics_in_t_e_vol3/abstracts/catapano_01.pdf Chang et al.5

  6. Current State of Liver TE2 • Pgusighisghsdg

  7. Room for Improvement • Pgusighisghsdg

  8. Room for Improvement • Pgusighisghsdg

  9. Future of Liver TE6 • Goals for development • Artificial liver • Used to study disease progression models • Bio-artificial liver • Hope for Acute Liver Failure patients • Use of viable cell sources • Primary porcine hepatocytes – most common7 • Relatively low cost, increase availability, safe • Progenitor stem cells → functional hepatocytes8 • Control, differentiation and proliferation • Promote phenotypic stability and tissue morphogenesis

  10. Future of Liver TE6 • Extracorporeal bioartificial liver Devices • Bidirectional mass transport • Stable microenviornment • Hepatocytes require specific environment to maintain function8 • Scale Up • Examples: • Hollow fiber devices, Flat plate systems, perfusion bed/ scaffolds, suspension and encapsulation8

  11. References • Hilsden, R.J., Shaffer, E.A. Chapter 14: The Liver, 1. Liver Structure and Function. First Principles of Gastroenterology: the basis of Disease and an Approach to Management. Canadian Association Pf Gastroenterology. 1994. • Shakesheff, K. Chapter 19: Liver Tissue Engineering. Tissue Engineering Using Ceramics and Polymers. London: Woodhead Publishing limited, 2007. • Abu-Absi, S.F., Friend, J. R., Hansen L. K., Hu W.S. Structural Polarity and Functional Bile Canaliculi in Rat Hepatocyte Spheroids. Experimental Cell Research. 274, 56, 2002. • Du, Y., Han, R. Wen, F., San, S.N.S., Xia, L., Wohland, T., Leo, H.L., Yu, H. Synthetic Sandwich culture of 3D Hepatocyte Monolayer. Biomaterials. 29, 290, 2008. • Chang, R. Nam, J., Sun, W. Computer-Aided Design, Modeling, and Freeform Fabrication of 3D Tissue Constructs for Drug Metabolism Studies. Computer-Aided Design and Applications. 5, 363, 2008. • Gerlach, J.C., Zeilinger, K., Patzer, J.F. II. Bioartificial Liver Systems: Why, What, Whither? Regenerative Medicine. 3, 575, 2008. • Behnia, K., Bhatia, S., Jastromb, N., Balis, U., Sullivan, S., Yarmush, M., Toner, M. Xenobiotic Metabolism by Cultured Primary Porcine Hepatocytes. Tissue Engineering. 6, 467, 2000. • Allen, J.W., Bhatia S. N. Engineering Liver Therapies for the Future. Tissue Engineering. 8, 725, 2002.

  12. Questions? Olga Filippova, Munir Nahri, Akash Patel BMES 471

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