Cord blood derived regulatory t cells a novel cure for graft versus host disease
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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

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

Siddharth Damania

2007



Bone marrow and stem cell transplants
Bone-Marrow and Stem-Cell Transplants

6,000 Americans

http://www.vacationusarentals.com/images/usa_map.gif


Bone marrow and stem cell transplants1
Bone-Marrow and Stem-Cell Transplants

http://www.southalabama.edu/nursing/MSN%20Info/surgery_nurse.jpg


Bone marrow and stem cell transplants2
Bone-Marrow and Stem-Cell Transplants

Over half develop GVHD

http://www.southalabama.edu/nursing/MSN%20Info/surgery_nurse.jpg


Graft versus host disease gvhd
Graft-Versus-Host-Disease (GVHD)

  • GVHD occurs when transplanted cells reject host cells in the patient

Transplanted

Cell

Patient Cell


Purpose
Purpose

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

GVHD

GVHD

GVHD

GVHD

GVHD


First goal
First Goal

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


Types of t cells
Types of T cells

  • Cytotoxic T cells

  • Helper T cells

  • T-reg cells

http://www.britannica.com/eb/art/print?id=85110&articleTypeId=0


Cd4 25 t reg cells
CD4+25+ T-reg Cells

  • Sakaguchi (2005)

    • Increased capability to suppress immune responses

    • Low numbers increase risk of autoimmune diseases


Cd4 25 t reg cells1
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


Umbilical cord blood
Umbilical Cord Blood

  • Godfrey et al (2005)

    • T-reg cells isolated from peripheral blood are often impure and require multiple purification processes


Umbilical cord blood1
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






Procedure4
Procedure

CD4+25+T-reg Cells


Facs t reg cell purity cd4 cd25
FACS T-reg Cell Purity (CD4/CD25)

86.2%

95.4%

91.5%

81.0%


Second goal
Second Goal

  • To culture derived CD4+25+ T-reg cells


Second goal1
Second Goal

  • To culture derived CD4+25+ T-reg cells

CD4+25+T-reg Cells


Second goal2
Second Goal

  • To culture derived CD4+25+ T-reg cells

CD4+25+T-reg Cells


Second goal3
Second Goal

  • To culture derived CD4+25+ T-reg cells

CD4+25+T-reg Cells

CD4+25+T-reg Cells








Third goal
Third Goal

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




Procedure7
Procedure

GVHD

GVHD

GVHD

GVHD

GVHD


Procedure8
Procedure

GVHD

GVHD

GVHD

GVHD

GVHD


Procedure9
Procedure

GVHD

GVHD

GVHD

GVHD

GVHD















Future work
Future Work

  • Optimize culture expansion


Future work1
Future Work

  • Optimize culture expansion

  • Increase rate of cure in mice


Future work2
Future Work

  • Optimize culture expansion

  • Increase rate of cure in mice

  • Test T-reg cells as a therapeutic cure for GVHD in humans


Acknowledgements
Acknowledgements

  • Dr. Keli Hippen

  • Dr. Paul Harker-Murray

  • The University of Minnesota

  • Lois Fruen

  • Advanced Science Research


Cord blood derived regulatory t cells a novel cure for graft versus host disease1

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

Siddharth Damania

2007


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