1 / 10

Headways in Liver Tissue Engineering

Headways in Liver Tissue Engineering. Olga Filippova, Munir Nahri, Akash Patel BMES 471. Anatomy of the Liver. Most metabolically complex organ 2 main, 2 smaller lobes Eight segments Lobules Dual blood supply Portal vein (75%) Hepatic artery (25%) Sinusoidal hepatocyte plates

idania
Download Presentation

Headways in Liver Tissue Engineering

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Headways in Liver Tissue Engineering Olga Filippova, Munir Nahri, Akash Patel BMES 471

  2. Anatomy of the Liver • Most metabolically complex organ • 2 main, 2 smaller lobes • 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 Liver • Metabolism • Glucose regulation • Drug neutralization • Amino acid catabolism • 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 TE Regeneration - One of few organs - 80% hepatectomy – full revovery Yokoyama et al.3 In Situ Regeneration - Vascularization for better hepatocyte transplant viability - Stable liver cell transplants under mice kinder capsule Yokoyama et al.3

  5. Current State of Liver TE Multi-cellular Aggregates • Improve homotypic aggregation • Replace generic lines • Co-cultures of non-parenchymal cells • Sinusoidal endothelial, stellate, etc. Abu-Absi et al.4 • Scaffolds • Improved architectural template • Alginate • Fully encapsulated hepatocyte cell lines Du et al.5

  6. Current State of Liver TE • Microtechnology and Cell Patterning • Microscale architecture for lobule models • Combined microfabrication and microcontact printing • Microfluidic structures mimicking liver sinusoids Bioreactors • Zoning of hepatocyte function • Improved oxygen and nutrient delivery • Enhanced viability and functionality for transportation • Miniaturization for higher throughput assay http://www.oulu.fi/spareparts/ebook_topics_in_t_e_vol3/abstracts/catapano_01.pdf Chang et al.5

  7. Room for Improvement Worldwide Prevalence of Liver Disease • Current systems maintain simple liver functions but lose complex • Function zones • mimicking anatomical structure • Recreating complex spatial and flow relationships • Animal models for live therapy evaluation • Limited human and stem cell supply • Primary cells preferred for therapy (2004)

  8. Future of Liver TE • Focused Federal Agency Collaborative • Progenitor stem cells • Controlled differentiation and proliferation • Phenotypic stability • Multiple cells types • Bioartificial Liver • Restore natural function • Vascular network – oxygen, nutrients • Bidirectional mass transport • Fully functional implantable TE liver

  9. 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. • Yokoyama, T., Ohashi, K., Kuge, H., Kanehiro, H., Iwata, H., Yamato, M., Nakajima, Y. In vivo engineering of metabolically active hepatic tissues in aneovascularized subcutaneous cavity. American Journal of Transplantation. 6, 50, 2006. • 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. • Cortesini, R. Stem cells, tissue engineering and organogenesis in transplantation. Transplant Immunology. 15, 81, 2005. • Allen, J.W., Bhatia S. N. Engineering Liver Therapies for the Future. Tissue Engineering. 8, 725, 2002.

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

More Related