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Cord Blood-Derived Regulatory T Cells: A Novel Cure for Graft-Versus-Host-Disease

Cord Blood-Derived Regulatory T Cells: A Novel Cure for Graft-Versus-Host-Disease. Siddharth Damania 2007. University of Minnesota Cancer Center. Bone-Marrow and Stem-Cell Transplants. 6,000 Americans. http://www.vacationusarentals.com/images/usa_map.gif.

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Cord Blood-Derived Regulatory T Cells: A Novel Cure for Graft-Versus-Host-Disease

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  1. Cord Blood-Derived Regulatory T Cells:A Novel Cure for Graft-Versus-Host-Disease Siddharth Damania 2007

  2. University of MinnesotaCancer Center

  3. Bone-Marrow and Stem-Cell Transplants 6,000 Americans http://www.vacationusarentals.com/images/usa_map.gif

  4. Bone-Marrow and Stem-Cell Transplants http://www.southalabama.edu/nursing/MSN%20Info/surgery_nurse.jpg

  5. Bone-Marrow and Stem-Cell Transplants Over half develop GVHD http://www.southalabama.edu/nursing/MSN%20Info/surgery_nurse.jpg

  6. Graft-Versus-Host-Disease (GVHD) • GVHD occurs when transplanted cells reject host cells in the patient Transplanted Cell Patient Cell

  7. Purpose • To use T-reg cells to cure mice with human GVHD GVHD GVHD GVHD GVHD GVHD

  8. First Goal • To devise a new protocol to derive and purify CD4+25+ T-reg cells using human umbilical cord blood

  9. Types of T cells • Cytotoxic T cells • Helper T cells • T-reg cells http://www.britannica.com/eb/art/print?id=85110&articleTypeId=0

  10. CD4+25+ T-reg Cells • Sakaguchi (2005) • Increased capability to suppress immune responses • Low numbers increase risk of autoimmune diseases

  11. CD4+25+ T-reg Cells • Sakaguchi (2005) • Increased capability to suppress immune responses • Low numbers increase risk of autoimmune diseases • Suri-Payer et al (2006) • Potential to suppress multiple types of autoimmune diseases

  12. Umbilical Cord Blood • Godfrey et al (2005) • T-reg cells isolated from peripheral blood are often impure and require multiple purification processes

  13. Umbilical Cord Blood • Godfrey et al (2005) • T-reg cells isolated from peripheral blood are often impure and require multiple purification processes • Umbilical cord blood facilitates easier purification and presents purer quantities of T-reg cells

  14. Procedure

  15. Procedure

  16. Procedure

  17. Procedure

  18. Procedure CD4+25+T-reg Cells

  19. FACS T-reg Cell Purity (CD4/CD25) 86.2% 95.4% 91.5% 81.0%

  20. Second Goal • To culture derived CD4+25+ T-reg cells

  21. Second Goal • To culture derived CD4+25+ T-reg cells CD4+25+T-reg Cells

  22. Second Goal • To culture derived CD4+25+ T-reg cells CD4+25+T-reg Cells

  23. Second Goal • To culture derived CD4+25+ T-reg cells CD4+25+T-reg Cells CD4+25+T-reg Cells

  24. 3/28 Cell Line

  25. KT32 Cell Line

  26. KT32-41BBL Cell Line

  27. KT32-OX40L Cell Line

  28. Culture Expansion of T-reg Cells

  29. Culture Decline of T-reg Cells

  30. Third Goal • To analyze the histological effect of CD4+25+ T-reg cells in GVHD mice

  31. Procedure

  32. Procedure

  33. Procedure GVHD GVHD GVHD GVHD GVHD

  34. Procedure GVHD GVHD GVHD GVHD GVHD

  35. Procedure GVHD GVHD GVHD GVHD GVHD

  36. Healthy Liver

  37. Diseased Liver

  38. Diseased Liver

  39. Diseased Liver

  40. Diseased Liver

  41. Diseased Liver

  42. GVHD Reduction with T-reg Cells

  43. GVHD Reduction with T-reg Cells

  44. GVHD Reduction with T-reg Cells

  45. GVHD Reduction with T-reg Cells 50%

  46. GVHD Reduction with T-reg Cells 44%

  47. GVHD Reduction with T-reg Cells 20%

  48. GVHD Reduction with T-reg Cells 45%

  49. Future Work • Optimize culture expansion

  50. Future Work • Optimize culture expansion • Increase rate of cure in mice

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