لخّصلي

Introduction: Despite the clinical success in vascularized composite allotransplantation (VCA), systemic immunosuppression remains necessary to prevent allograft rejection.Conclusion: Despite the demonstrated feasibility of VCA in recent years, continued im?provements to immunomodulatory strategies using tools like clustered regularly inter?spaced short palindromic repeats/Cas9 could lead to the development of approaches that mitigate the limitations associated with rejection of this life-giving procedure.a 2023 Elsevier Inc.In this context, genomic editing has emerged as a potential tool to minimize the need for toxic immunosuppressive regimens and has gained attention in the fields of solid organ transplantation and xeno?transplantation.All rights reserved.

Introduction: Despite the clinical success in vascularized composite allotransplantation
(VCA), systemic immunosuppression remains necessary to prevent allograft rejection.
Even with potent immunosuppressive regimens (tacrolimus, mycophenolate mofetil, and
steroids), most patients experience several rejection episodes, often within the same year.
The risk of systemic side effects must constantly be weighed against the risk of under￾immunosuppression and, thus, acute and chronic rejection. In this context, genomic
editing has emerged as a potential tool to minimize the need for toxic immunosuppressive
regimens and has gained attention in the fields of solid organ transplantation and xeno￾transplantation. This strategy may also be relevant for the future of VCA.
Methods: We discuss the topic of genetic engineering and review recent developments in
this field that justify investigating tools such as clustered regularly interspaced short
palindromic repeats/Cas9 in the context of VCA.
Results: We propose specific strategies for VCA based on the most recent gene expression
data. This includes the well-known strategy of tolerance induction. Specifically, targeting
the interaction between antigen-presenting cells and recipient-derived T cells by CD40
knockout may be effective. The novelty for VCA is a discovery that donor-derived T lym￾phocytes may play a special role in allograft rejection of facial transplants. We suggest
targeting these cells prior to transplantation (e.g., by ex vivo perfusion of the transplant) by
knocking out genes necessary for the long-term persistence of donor-derived immune cells
in the allograft.
Conclusion: Despite the demonstrated feasibility of VCA in recent years, continued im￾provements to immunomodulatory strategies using tools like clustered regularly inter￾spaced short palindromic repeats/Cas9 could lead to the development of approaches that
mitigate the limitations associated with rejection of this life-giving procedure.
ª 2023 Elsevier Inc. All rights reserved.