Stable mixed chimerism and tolerance using a nonmyeloablative preparative regimen in a large-animal model

Christene A. Huang, Yasushi Fuchimoto, Rachel Scheier-Dolberg, Michael C. Murphy, David M. Neville, David H. Sachs

研究成果: Article査読

177 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)173-181
ページ数9
ジャーナルJournal of Clinical Investigation
105
2
DOI
出版ステータスPublished - 2000 1
外部発表はい

ASJC Scopus subject areas

  • 医学(全般)

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