Exploring cell-based tolerance strategies for hand and face transplantation

Abstract

Broader clinical application of reconstructive hand and face transplantation is hindered by the need for lifelong immunosuppression for allograft maintenance. In this review, we summarize various cell-based approaches to tolerance induction currently under investigation in both clinical and pre-clinical models to alleviate the need for chronic immunosuppression. These include strategies to induce mixed hematopoietic chimerism, therapy with T and B regulatory cells, regulatory macrophages, tolerogenic dendritic cells, and mesenchymal stem cells. The vascularized, intragraft bone components inherent to reconstructive transplants serve as a continuous source of donor-derived hematopoietic cells, and make hand and face transplants uniquely well suited for cell-based approaches to tolerance that may ultimately tilt the risk-benefit balance for these life-changing, but not life-saving, procedures.

The intragraft vascularized bone marrow component plays a critical role in tolerance induction after reconstructive transplantation

“…6 Particularly appealing for overcoming this dilemma are various cell-based approaches to induce mixed chimerism and transplant tolerance. [7][8][9][10] This is conventionally accomplished with transplantation of donor-derived BM cells to the recipient to induce chimerism. [11][12][13] Conditioning therapies with less toxicity can now be used with adjunctive allogeneic BM transplantation.…”

Nasal Unit Transplantation: A Cadaveric Anatomical Feasibility Study

“…Although vascularized composite allotransplantation (VCA) in its current state necessitates acceptance of the risks inherent with lifelong immunosuppression, need for close long-term follow-up, 19 and the possibility of chronic rejection in transplanted facial subunits, 20,21 transplantation of isolated nasal units may afford opportunities to advance immunologic understanding of composite transplant biology [22][23][24] with relatively reduced risk to patients. Although there is no question that the immunosuppression required for VCA introduces short-and long-term risks to the patient, it is also increasingly apparent that contemporary approaches hold significant promise at mitigating these risks, offering the potential to rebalance the risk-benefit ratio in favor of the intervention.…”

“…In this regard and in light of the various side effects and toxicities associated with chronic multidrug immunosuppression, VCA teams around the world are developing novel, innovative therapeutic concepts of immunoregulation to reduce systemic immunosuppression to minimal levels or weaning patients off immunosuppression altogether. 24,26 Similarly, recent advances in cell-based therapies and immunosuppressive drug development that incorporate the unique elements and biology of composite tissue grafts have also shown favorable results at achieving this goal. 27,28 Clearly, the induction of donor-specific tolerance would obviate the need for long-term maintenance immunosuppression after VCA and great strides in this regard have currently been made in translational large animal models of VCA.…”

Reflections on a Decade of Face Transplantation

“…Many groups all over the world should be commended for their remarkable contribution to the field. 7,8,[37][38][39] A comprehensive review of these achievements or of current experimental hurdles goes beyond the scope of this article and can be found elsewhere. 10 Authors believe, however, that the 3 most relevant investigative areas to focus on are strategies to induce immunological tolerance to VCAs, development of less toxic immunosuppressive therapies, and the establishment of noninvasive monitoring methods to predict and intercept complications (acute/chronic rejection).…”