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

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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

University of MinnesotaCancer Center


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


Procedure

Procedure


Procedure1

Procedure


Procedure2

Procedure


Procedure3

Procedure


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


3 28 cell line

3/28 Cell Line


Kt32 cell line

KT32 Cell Line


Kt32 41bbl cell line

KT32-41BBL Cell Line


Kt32 ox40l cell line

KT32-OX40L Cell Line


Culture expansion of t reg cells

Culture Expansion of T-reg Cells


Culture decline of t reg cells

Culture Decline of T-reg Cells


Third goal

Third Goal

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


Procedure5

Procedure


Procedure6

Procedure


Procedure7

Procedure

GVHD

GVHD

GVHD

GVHD

GVHD


Procedure8

Procedure

GVHD

GVHD

GVHD

GVHD

GVHD


Procedure9

Procedure

GVHD

GVHD

GVHD

GVHD

GVHD


Healthy liver

Healthy Liver


Diseased liver

Diseased Liver


Diseased liver1

Diseased Liver


Diseased liver2

Diseased Liver


Diseased liver3

Diseased Liver


Diseased liver4

Diseased Liver


Gvhd reduction with t reg cells

GVHD Reduction with T-reg Cells


Gvhd reduction with t reg cells1

GVHD Reduction with T-reg Cells


Gvhd reduction with t reg cells2

GVHD Reduction with T-reg Cells


Gvhd reduction with t reg cells3

GVHD Reduction with T-reg Cells

50%


Gvhd reduction with t reg cells4

GVHD Reduction with T-reg Cells

44%


Gvhd reduction with t reg cells5

GVHD Reduction with T-reg Cells

20%


Gvhd reduction with t reg cells6

GVHD Reduction with T-reg Cells

45%


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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