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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZRG1-BCMB-A (52))
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Kraemer, Kristy A
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Stanford University
Internal Medicine/Medicine
Schools of Medicine
United States
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Kooreman, Nigel G; de Almeida, Patricia E; Stack, Jonathan P et al. (2017) Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics. Cell Rep 20:1978-1990
Calderon, D; Prot, M; You, S et al. (2016) Control of Immune Response to Allogeneic Embryonic Stem Cells by CD3 Antibody-Mediated Operational Tolerance Induction. Am J Transplant 16:454-67
Riegler, Johannes; Tiburcy, Malte; Ebert, Antje et al. (2015) Human Engineered Heart Muscles Engraft and Survive Long Term in a Rodent Myocardial Infarction Model. Circ Res 117:720-30
Pan, Yuqiong; Leveson-Gower, Dennis B; de Almeida, Patricia E et al. (2015) Engraftment of embryonic stem cells and differentiated progeny by host conditioning with total lymphoid irradiation and regulatory T cells. Cell Rep 10:1793-802
de Almeida, Patricia E; Meyer, Everett H; Kooreman, Nigel G et al. (2014) Transplanted terminally differentiated induced pluripotent stem cells are accepted by immune mechanisms similar to self-tolerance. Nat Commun 5:3903
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
Pearl, Jeremy I; Kean, Leslie S; Davis, Mark M et al. (2012) Pluripotent stem cells: immune to the immune system? Sci Transl Med 4:164ps25
Gold, Joseph D; Wu, Joseph C (2012) Returns of the living dead: therapeutic action of irradiated and mitotically inactivated embryonic stem cells. Circ Res 111:1250-2
Sanchez-Freire, Veronica; Ebert, Antje D; Kalisky, Tomer et al. (2012) Microfluidic single-cell real-time PCR for comparative analysis of gene expression patterns. Nat Protoc 7:829-38

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