Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 105, Issue 2, Pages 173-181Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI7913
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Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL046532, R01HL063430] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [Z01MH002747] Funding Source: NIH RePORTER
- NHLBI NIH HHS [1RO1 HL-63430, 5RO1 HL-46532] Funding Source: Medline
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Bone marrow transplantation (BMT) has considerable potential for the treatment of malignancies, hemoglobinopathies, and autoimmune diseases, as well as the induction of transplantation allograft tolerance. Toxicities associated with standard preparative regimens for bone marrow transplantation, however make this approach unacceptable for all but the most severe of these clinical situations. Here, we demonstrate that stable mixed hematopoietic cell chimerism and donor-specific tolerance can be established in miniature swine, using a relatively mild, non-myeloablative preparative regimen. We conditioned recipient swine with whole-body and thymic irradiation, and we depleted their T-cells by CD3 immunotoxin-treatment. Infusion of either bone marrow cells or cytokine-mobilized peripheral blood stem cells from leukocyte antigen-matched animals resulted in stable mixed chimerism, as detected by flow cytometry in the peripheral blood, thymus, and bone marrow, without any clinical evidence of graft-versus-host disease (GvHD). Long-term acceptance of donor skin and consistent rejection of third-party skin indicated that the recipients had developed donor-specific tolerance.
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