Before human embryonic stem (hES) cell-based therapies (e.g., for such conditions as neuronal disease, cardiovascular disease, diabetes, Parkinson's, among others) can be translated into the clinic, we must develop new strategies that can overcome the immunological barrier. To address this critical bottleneck, we have assembled an interdisciplinary team of investigators who are focused on developing novel and effective strategies to induce immunological tolerance for hES cell therapy. Our ability to overcome the immunological response will be a major scientific advance in stem cell biology.

Public Health Relevance

The goal of our T-R01 proposal is to re-educate the immune system toward achieving tolerance of hES cell-based therapies by combining hematopoietic chimerism and thymic regeneration. We have assembled an interdisciplinary team of established investigators with complementary experiences. Here we seek to characterize the immunological profiles of hES cells in an allogeneic humanized mouse model;to demonstrate the effectiveness of co-stimulatory blockade strategies for induction of peripheral tolerance to hES cells;and to develop an innovative approach for central tolerance with hemaopoietic chimerism and thymic regeneration. If successful, this achievement will represent a major scientific advancement in hES cell immunology and a significant step toward their eventual clinical translation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI085575-04
Application #
8316183
Study Section
Special Emphasis Panel (ZRG1-BCMB-A (52))
Program Officer
Kraemer, Kristy A
Project Start
2009-09-25
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$392,329
Indirect Cost
$147,304
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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Huber, Bruno C; Ransohoff, Julia D; Ransohoff, Katherine J et al. (2013) Costimulation-adhesion blockade is superior to cyclosporine A and prednisone immunosuppressive therapy for preventing rejection of differentiated human embryonic stem cells following transplantation. Stem Cells 31:2354-63
de Almeida, Patricia E; Ransohoff, Julia D; Nahid, Abu et al. (2013) Immunogenicity of pluripotent stem cells and their derivatives. Circ Res 112:549-61
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