Recipient bone marrow engraftment in donor tissue after long-term tolerance to a composite tissue allograft

David W. Mathes, Mark A. Randolph, Judy L. Bourget, G. Petur Nielsen, Vincent R. Ferrera, J. Scott Arn, David H. Sachs, W P Andrew Lee

Research output: Contribution to journalArticle

Abstract

Background. An important component of a composite tissue limb allograft (CTA) is the vascularized bone marrow and bone marrow stroma, which when transplanted could create immediate marrow space and engraftment. We have previously demonstrated that tolerance to musculoskeletal allografts can be achieved with a 12-day course of cyclosporine without the presence of long-term peripheral donor cell chimerism. The objective of this study was to determine the fate of the donor bone marrow after transplantation of a limb allograft in a miniature swine model. Methods. CTAs from donor swine were heterotopically transplanted into six MHC-matched, minor-antigen-mismatched recipients, and a 12-day course of cyclosporine was given. Previous animals transplanted without cyclosporine rejected their grafts in less than 42 days. A non-MHC-linked marker, pig allelic antigen (PAA), was used to distinguish host and donor cells. Three PAA- animals received PAA+ CTAs, and three PAA+ animals received PAA- CTAs. Bone marrow was harvested from the donor limb grafts and the recipient and analyzed by flow cytometry and histology. Thymus, spleen, and mesenteric lymph nodes were also harvested from the recipient swine and evaluated for the presence of donor cells by flow cytometry. Results. All animals receiving cyclosporine demonstrated permanent tolerance to their allografts. Donor bone marrow cells were present in all grafts at the time of transplantation and during the immediate postoperative period. By 48 weeks, donor cells were no longer detectable within the marrow space of the allograft. In long-term animals host bone marrow cells replaced donor cells in the graft marrow space. No evidence of donor cell engraftment was found in recipient animals. Conclusion. This study demonstrates that in long-term tolerant recipients of musculoskeletal allografts there is no evidence of persistent donor bone marrow cells in the hematopoietic tissues of the graft or the host. Rather, the recipient's bone marrow cells and lymphocytes repopulate the donor marrow space of the graft.

Original languageEnglish (US)
Pages (from-to)1880-1885
Number of pages6
JournalTransplantation
Volume73
Issue number12
StatePublished - Jun 27 2002
Externally publishedYes

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Composite Tissue Allografts
Swine
Bone Marrow
Tissue Donors
Allografts
Transplants
Antigens
Bone Marrow Cells
Cyclosporine
Extremities
Flow Cytometry
Miniature Swine
Chimerism
Bone Marrow Transplantation
Postoperative Period
Thymus Gland
Histology
Spleen
Transplantation
Lymph Nodes

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Mathes, D. W., Randolph, M. A., Bourget, J. L., Nielsen, G. P., Ferrera, V. R., Arn, J. S., ... Lee, W. P. A. (2002). Recipient bone marrow engraftment in donor tissue after long-term tolerance to a composite tissue allograft. Transplantation, 73(12), 1880-1885.

Recipient bone marrow engraftment in donor tissue after long-term tolerance to a composite tissue allograft. / Mathes, David W.; Randolph, Mark A.; Bourget, Judy L.; Nielsen, G. Petur; Ferrera, Vincent R.; Arn, J. Scott; Sachs, David H.; Lee, W P Andrew.

In: Transplantation, Vol. 73, No. 12, 27.06.2002, p. 1880-1885.

Research output: Contribution to journalArticle

Mathes, DW, Randolph, MA, Bourget, JL, Nielsen, GP, Ferrera, VR, Arn, JS, Sachs, DH & Lee, WPA 2002, 'Recipient bone marrow engraftment in donor tissue after long-term tolerance to a composite tissue allograft', Transplantation, vol. 73, no. 12, pp. 1880-1885.
Mathes DW, Randolph MA, Bourget JL, Nielsen GP, Ferrera VR, Arn JS et al. Recipient bone marrow engraftment in donor tissue after long-term tolerance to a composite tissue allograft. Transplantation. 2002 Jun 27;73(12):1880-1885.
Mathes, David W. ; Randolph, Mark A. ; Bourget, Judy L. ; Nielsen, G. Petur ; Ferrera, Vincent R. ; Arn, J. Scott ; Sachs, David H. ; Lee, W P Andrew. / Recipient bone marrow engraftment in donor tissue after long-term tolerance to a composite tissue allograft. In: Transplantation. 2002 ; Vol. 73, No. 12. pp. 1880-1885.
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AU - Lee, W P Andrew

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