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Assessing the Viability of Islet Xeno -Transplants for Type-1 Diabetes

Assessing the Viability of Islet Xeno -Transplants for Type-1 Diabetes . Madelaine Taft-Ferguson (2008-2009). Background: Islet Transplant. http:// www.cornellmedicine.com/research/islet/img/diagram.jpg. Islet Transplant. http:// www.cornellmedicine.com/research/islet/img/diagram.jpg.

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Assessing the Viability of Islet Xeno -Transplants for Type-1 Diabetes

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  1. Assessing the Viability of Islet Xeno-Transplants for Type-1 Diabetes Madelaine Taft-Ferguson (2008-2009)

  2. Background: Islet Transplant http://www.cornellmedicine.com/research/islet/img/diagram.jpg

  3. Islet Transplant http://www.cornellmedicine.com/research/islet/img/diagram.jpg

  4. Islet Transplant http://www.cornellmedicine.com/research/islet/img/diagram.jpg

  5. Islet Transplant http://www.cornellmedicine.com/research/islet/img/diagram.jpg

  6. Goals: Allo- vs. Xeno-Transplant Allo Xeno Human : http://upload.wikimedia.org/wikipedia/commons/thumb/1/17/Human_outline.svg/270px-Human_outline.svg.png Pig (modified) : http://mischiefmari.files.wordpress.com/2006/12/the-pig.jpg

  7. Background: Immune Response Healthy Sick Perforin Granzyme B TRAIL IFNg IL-17 Human: http://www.atsdr.cdc.gov/training/public-health-assessment-overview/html/module3/images_s5/body.gif

  8. Proteins in Immune Response • Perforin • Granzyme B • IFNg • IL-17 • TRAIL

  9. Procedure: ICS = Perforin, Granzyme B, TRAIL, IFNg, or IL-17 T-cell

  10. Intracellular Cytometric Staining = Perforin, Granzyme B, TRAIL, IFNg, or IL-17 T-cell Permed

  11. Intracellular Cytometric Staining = Perforin, Granzyme B, TRAIL, IFNg, or IL-17 T-cell Antibody-conjugated dye

  12. Intracellular Cytometric Staining = Perforin, Granzyme B, TRAIL, IFNg, or IL-17 T-cell Detected with flow cytometer

  13. Results: Perforin CD4 CD8

  14. Results: Granzyme B CD4 CD8

  15. Results: IL-17 CD4 CD8

  16. Results: IFNg CD4 CD8

  17. Results: TRAIL CD4 CD8

  18. Conclusions • Xeno-stimulation induces a different immune response than does allo-stimulation • New immunosuppressive drugs are needed for suppression of xeno-stimulated responses • Weak perforin/granzyme B (CD8+) response • Strong inflammatory response (CD4+) • Presence of TRAIL

  19. Limitations & Future Work • Sample size • Verify conclusions on immune response differences • Investigate TRAIL mechanism in CD4+ cells • Develop new immunosuppressive drugs

  20. Acknowledgements • PratimaBansal-Pakala, Ph.D • Kelly Hire • Diabetes Institute for Immunology and Transplantation • Lois Fruen • Science Research class Dr. Pakala: http://www.surg.umn.edu/surgery/Faculty_Alpha/bansalpakala_pratima.html Science Research: Photo by L. Fruen

  21. Assessing the Viability of Islet Xeno-Transplants for Type-1 Diabetes Madelaine Taft-Ferguson (2008-2009)

  22. Background: Perforin & Granzyme B • McKenzie, et al. (2006) • Perforin is the one of the primary means by which CD8+ cells kill islet cells • Sleater, et al. (2007) • In vitro, human islet cells are killed by perforin-negative cells

  23. Background: IL-17 & IFNg • Augustine, et al. (2005) and Bellisola, et al. (2006) • IFNgcorrelates with renal transplant failure • McKenzie, et al. (2007) • Perforin expression induced by IFNg • Diamond and Gill (2000) • IFNg“essential” in allo-transplant rejection

  24. Background: TRAIL • Ou, et al. (2002) • TRAIL kills beta cells • Sanlioglu , et al. (2008) • TRAIL correlates with pancreatic cell death

  25. Limitations • Granzyme B Unstimulated cells Allo-stimulated (day seven) CD4+cells CD8+cells

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