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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)173-181
Number of pages9
JournalJournal of Clinical Investigation
Volume105
Issue number2
Publication statusPublished - 2000 Jan
Externally publishedYes

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Transplantation Tolerance
Chimerism
Bone Marrow Transplantation
Animal Models
Miniature Swine
Immunotoxins
Hemoglobinopathies
Skin
Whole-Body Irradiation
Graft vs Host Disease
HLA Antigens
Bone Marrow Cells
Thymus Gland
Autoimmune Diseases
Flow Cytometry
Swine
Bone Marrow
Cytokines
T-Lymphocytes
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Huang, C. A., Fuchimoto, Y., Scheier-Dolberg, R., Murphy, M. C., Neville, D. M., & Sachs, D. H. (2000). Stable mixed chimerism and tolerance using a nonmyeloablative preparative regimen in a large-animal model. Journal of Clinical Investigation, 105(2), 173-181.

Stable mixed chimerism and tolerance using a nonmyeloablative preparative regimen in a large-animal model. / Huang, Christene A.; Fuchimoto, Yasushi; Scheier-Dolberg, Rachel; Murphy, Michael C.; Neville, David M.; Sachs, David H.

In: Journal of Clinical Investigation, Vol. 105, No. 2, 01.2000, p. 173-181.

Research output: Contribution to journalArticle

Huang, CA, Fuchimoto, Y, Scheier-Dolberg, R, Murphy, MC, Neville, DM & Sachs, DH 2000, 'Stable mixed chimerism and tolerance using a nonmyeloablative preparative regimen in a large-animal model', Journal of Clinical Investigation, vol. 105, no. 2, pp. 173-181.
Huang CA, Fuchimoto Y, Scheier-Dolberg R, Murphy MC, Neville DM, Sachs DH. Stable mixed chimerism and tolerance using a nonmyeloablative preparative regimen in a large-animal model. Journal of Clinical Investigation. 2000 Jan;105(2):173-181.
Huang, Christene A. ; Fuchimoto, Yasushi ; Scheier-Dolberg, Rachel ; Murphy, Michael C. ; Neville, David M. ; Sachs, David H. / Stable mixed chimerism and tolerance using a nonmyeloablative preparative regimen in a large-animal model. In: Journal of Clinical Investigation. 2000 ; Vol. 105, No. 2. pp. 173-181.
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