Bone marrow transplantation from α1,3-galactosyltransferase gene-knockout pigs in baboons

Y. L. Tseng, F. J.M.F. Dor, K. Kuwaki, D. Ryan, J. Wood, M. Denaro, M. Giovino, K. Yamada, R. Hawley, C. Patience, H. J. Schuurman, M. Awwad, D. H. Sachs, D. K.C. Cooper

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38 Citations (Scopus)

Abstract

Background: Successful hematopoietic cell allotransplantation results in donor-specific tolerance, but this approach has been unsuccessful in the wild-type pig-to-baboon xenotransplantation model, as pig cells were lost from the circulation within 5 days. However, after cessation of immunosuppressive therapy on day 28, all baboons demonstrated non-specific unresponsiveness on mixed leukocyte reaction (MLR) for at least 30 days. We have now investigated the transplantation of bone marrow (BM) cells from miniature swine homozygous for α1,3-galactosyltransferase gene-knockout (GalT-KO). Methods: Baboons (n = 3) were pre-treated with whole body and thymic irradiation, anti-thymocyte globulin, and splenectomy, and received immunosuppressive and supportive therapy for 28 days. BM was harvested from GalT-KO swine (n = 3). The baboons were monitored for the presence of pig cells by flow cytometry and colony-forming units (CFUs), and for cellular reactivity by MLR. Results: A mean of 11 × 108 BM cells/kg was infused into each baboon. The mean absolute numbers and percentages of pig cells detected in the blood at 2 h and on days. 1, 2 and 4, respectively, were 641/μl (9.5%), 132/μl (3.4%), 242/μl (3.9%), and 156/μl (2.9%). One baboon died (from accidental hemorrhage) on day 6, at which time chimerism was present in the blood (2.0%) and BM (6.4%); pig cell engraftment in the BM was confirmed by polymerase chain reaction (PCR) of CFUs. In the two other baboons, blood chimerism was lost after day 5 but returned at low levels (< 1%) between days 9 to 16 and 7 to 17, respectively, indicating transient BM engraftment. Both surviving baboons showed non-specific unresponsiveness on MLR until they were euthanized on days 85 and 110, respectively. Conclusions: By using BM cells from GalT-KO pigs, chimerism was detected at levels comparable with previous studies when 30-fold more growth factor-mobilized peripheral blood progenitor cells had been transplanted. In addition, cellular hyporesponsiveness was prolonged. However, long-term engraftment and chimerism were not achieved.

Original languageEnglish
Pages (from-to)361-370
Number of pages10
JournalXenotransplantation
Volume11
Issue number4
DOIs
Publication statusPublished - 2004 Jul

All Science Journal Classification (ASJC) codes

  • Immunology
  • Transplantation

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