More and more composite tissue grafts are worldwide performed. This kind of graft implies to take a sample of all necessary tissues and vascular and nervous elements for the reconstruction of a given area.

This includes elbow, arm, hand and face transplantations and requires surgical skill and a multidisciplinary approach. Because in these cases transplanted tissues are always coming from a genetically non-identical donor (allograft), they generate a rejection process mediated by the recipient immune system. Therefore, chronic immunosuppression is required to prevent rejection and graft loss, with some side effects that may limit the indication of transplantation based on logic of cost-benefit ratio. The ideal solution would be to get reliable protocols for inducing transplantation tolerance.

Very recently, funded by the Melina Nakos foundation and the First Elite program of the Walloon region, and in collaboration with Professor Frédéric Schuind from Erasme hospital, doctors Zanzhuo Li and Alain Le Moine, at the Institute for Medical Immunology Université libre de Bruxelles (ULB), developed a mouse model of composite tissue allograft including a vascularised femur.

The results of their research are published in the American Journal of Transplantation, the official journal of the American Society of Transplantation (AST).

In this model, a short course of immunosuppression at the time of transplantation allowed to make recipients robustly tolerant to the transplant. Importantly, tolerance was donor-specific, since recipients were still able to reject a third party allograft (unrelated to the donor), meaning that recipient immune system ultimately recovered responsiveness. It was shown that donor-type haematopoietic stem cells derived from the transplanted bone repopulated the recipient immune system and induced tolerance by removing anti-donor cells. This did not require recipient aggressive preconditioning which is considered as a too risky treatment to be applied in the context of composite tissue allografts. Therefore, vascularized bone transplantation containing donor-derived bone marrow cells might become a valuable tool for inducing transplantation tolerance in composite tissue allografts but also in other transplantations.

This study demonstrates the feasibility of stem cells grafts through a vascularised bone and the tolerance that it induces in the recipient of a composite tissue allograft.

In terms of clinical applications, this could be an alternative method to the intravenous injection of stem cells which does not induce a stable chimerism in the recipient unless after a heavy conditioning of the patient.

Zhanzhuo L, Benghiat FS, Kubjak C, Noval Rivas M, Cobbold S, Waldmann H, Petein M, Schuind F, Goldman M, Le Moine A. CD8+ T cell depletion and rapamycin synergize with signal 1 and 2 blockade to induce robust limb allograft tolerance in mice. Am J Transplant 2008 ; 8 : 1-10.

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