Presentation on theme: "The Liver is Super Super Awesome Olga Filippova, Munir Nahri, Akash Patel BMES 471."— Presentation transcript:
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 Endothelial, Kupffers, Fat-storing, Pit
- Metabolism - Glucose regulation - Amino acid catabolism - Drug neutralization - Bile synthesis - Digestion of fat - Cholesterol catabolism - Stored in gallbladder - Released by CCK from SI Functions of the Liver 1
Regeneration - One of few organs able to regenerate - Full functional recovery after 80% hepatectomy Current State of Liver TE 2 In Situ Regeneration - Vascularization for increasing hepatocyte trasplants in vivo - Ohashi et al. have developed a method to form stable transplants of liver cells under the kidney capsule in the mice Yokoyama, T., Ohashi, K., Kuge, H., Kanehiro, H., Iwata, H., Yamato, M. and Nakajima, Y. (2006) In vivo engineering of metabolically active hepatic tissues in a neovascularized subcutaneous cavity. American Journal of Transplantation, 6, 50± 59.
- Multicellular Aggregates - Improvements to the homotypic aggregation - Co-cultures replacing current generic lines with non-parenchymal cells - Sinusoidal endothelial, stellate, etc. Current State of Liver TE 2 Abu-Absi et al. 3 Du et al. 4 - Scaffolds - Provide improved architectural template - Alginate scaffolds - Including fully encapsulated hepatocyte cell lines
- Bioreactors -zonation of hepatocyte functioning. -improved delivery of oxygen and nutrients -enhanced viability and functionality if transportation is required -miniaturisation of engineered tissue for higher throughput assay Current State of Liver TE 2 Chang et al. 5 - Microtechnology and Cell Patterning -Building microscale architecture of liver lobule models -Combined microfabrication and microcontact printing -Microfluidic structures mimicking sinusoids of the liver
Simple functions of the liver may be maintained in current tissue- engineered liver systems, more complex functions are always lost Display zonal liver functions that mimic anatomical structure of liver Recreating complex spatial and flow relationships Development of predictive animal models to evaluate live therapies Limited supply of primary human cells – Primary human cells are preferred source of cellular therapies Room for Improvement Worldwide Prevalence of Liver Disease Annually
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Future of Liver TE 6 -Development of complex 3D Liver models -Artificial or Bioartificial Liver (BAL) -Vascular network capable of providing oxygen and nutrients to tissue  -Ability to restore liver natural function and able to maintain hemostasis -Capable of bidirectional mass transport -Optimal results -Mimic natural liver -Size of BAL -Spatial arrangement -Viable cell source -Progenitor stem cells Promote phenotypic stability and tissue morphogenesis  -Key success: -Ability to control differentiation and proliferation of stem cells -Proper signaling to introduce other key cells in liver regeneration -Ultimate goal fully functional tissue engineered implantable liver
-Extracorporeal bioartificial liver Devices -Bidirectional mass transport -Stable microenviornment -Hepatocytes require specific environment to maintain function 8 -Scale Up -Examples: -Hollow fiber devices, Flat plate systems, perfusion bed/ scaffolds, suspension and encapsulation 8 Future of Liver TE 6
1.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 Shakesheff, K. Chapter 19: Liver Tissue Engineering. Tissue Engineering Using Ceramics and Polymers. London: Woodhead Publishing limited, 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, 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, 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, Gerlach, J.C., Zeilinger, K., Patzer, J.F. II. Bioartificial Liver Systems: Why, What, Whither? Regenerative Medicine. 3, 575, 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, Allen, J.W., Bhatia S. N. Engineering Liver Therapies for the Future. Tissue Engineering. 8, 725, References
1.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 Gerlach, J.C., Zeilinger, K., Patzer, J.F. II. Bioartificial Liver Systems: Why, What, Whither? Regenerative Medicine. 3, 575, Cortesini, R. Stem cells, tissue engineering and organogenesis in transplantation. Transplant Immunology, 15, 81, Allen, J.W., Bhatia S. N. Engineering Liver Therapies for the Future. Tissue Engineering. 8, 725, 2002.
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