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.

Keywords:

• mesenchymal stem cell
• mixed chimerism
• regulatory B cell
• regulatory macrophage
• regulatory T cell
• tolerance
• tolerogenic dendritic cell
• vascularized composite allotransplantation

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Clinical applicability of non-lifesaving hand and face transplants is limited by the need for lifelong immunosuppression to maintain the allograft.

• Many cell-based approaches to tolerance induction are currently under investigation in both pre-clinical models and clinical trials.

• Regulatory T cells, B cells, and macrophages, along with tolerogenic dendritic cells and mesenchymal stem cells, have shown various levels of potential for immunomodulatory therapy in the context of allotransplantation.

• To date, mixed chimerism is the most successful cell-based approach to clinical allograft tolerance.

• The vascularized, intragraft bone component of hand and face allografts uniquely positions reconstructive transplantation in cell-based approaches to tolerance induction.