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Updated: Mar 11, 2026
A Modified Heterotopic Swine Hind Limb Transplant Model for Translational Vascularized Composite Allotransplantation VCA Research
Published on: October 14, 2013
Long-term Tolerance Toward Haploidentical Vascularized Composite Allograft Transplantation in a Canine Model Using
Jeff Chang1, Scott S Graves, Tiffany Butts-Miwongtum
11 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA. 2 Department of Surgery, University of Washington, Seattle, WA. 3 Department of Medicine, University of Washington, Seattle, WA. 4 Department of Pathology, University of Washington, Seattle, WA. 5 Department of Surgery, University of Colorado, Aurora, CO. 6 Plastic Surgery Service, VA Eastern Colorado Care System, Denver, CO.
Background:
The development of safe and reliable protocols for the transplantation of the face and hands may be accomplished with animal modeling of transplantation of vascularized composite allografts (VCA). Previously, we demonstrated that tolerance to a VCA could be achieved after canine recipients were simultaneously given marrow from a dog leukocyte antigen-identical donor. In the present study, we extend those findings across a dog leukocyte antigen mismatched barrier.
Methods:
Eight recipient dogs received total body irradiation (4.5 cGy), hematopoietic cell transplantation (HCT), either marrow (n = 4) or granulocyte-colony stimulating factor mobilized peripheral blood stem cells (n = 4), and a VCA transplant from the HCT donor. Post grafting immunosuppression consisted of mycophenolate mofetil (28 days) and cyclosporine (35 days).
Results:
In 4 dogs receiving bone marrow, 1 accepted both its marrow transplant and demonstrated long-term tolerance to the donor VCA (>52 weeks). Three dogs rejected both their marrow transplants and VCA at 5 to 7 weeks posttransplant. Dogs receiving mobilized stem cells all accepted their stem cell transplant and became tolerant to the VCA. However, 3 dogs developed graft-versus-host disease, whereas 1 dog rejected its stem cell graft by week 15 but exhibited long-term tolerance toward its VCA (>90 weeks).
Conclusions:
The data suggest that simultaneous transplantation of mobilized stem cells and a VCA is feasible and leads to tolerance toward the VCA in a haploidentical setting. However, there is a higher rate of donor stem cell engraftment compared with marrow HCT and an increase in the incidence of graft-versus-host disease.
