Journal ArticleDOI
Vascularized composite allotransplantation: towards tolerance and the importance of skin-specific immunobiology.
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TLDR
Current immunosuppressive regimens for VCA are reviewed, progress with immunomodulatory and tolerance protocols are highlighted, and recent advances in cutaneous immunobiology are highlighted which will have significant implications for future development in the field.Abstract:
Purpose of review Vascularized composite allotransplantation (VCA) is increasingly utilized in the restoration of complex injuries and tissue loss. Acute skin-targeted rejection episodes are common and concerns remain regarding the risks of conventional immunosuppression. We review current immunosuppressive regimens for VCA, progress with immunomodulatory and tolerance protocols, and highlight recent advances in cutaneous immunobiology which will have significant implications for future development in the field. Recent findings Advances in induction protocols have demonstrated effective prevention of early graft loss in hand transplantation, although long-term outcomes are still pending. Furthermore, recent findings in leukocyte populations within the skin and their mechanisms of communication reveal that considerable numbers of resident T-effector memory cells, including a T-regulatory subset, exist, and that epidermal Langerhans' cells communicate with these cells, mediating both immunity and tolerance to maintain skin homeostasis. Summary The majority of VCA centers utilize antibody-mediated induction, followed by double or triple-agent maintenance immunosuppression. A clinical trial of a minimal-immunosuppression protocol based on bone marrow infusion reports encouraging interim results, but long-term follow-up will be required. Skin remains the primary target of rejection in VCA. New data demonstrate extensive T-cell memory resident in skin, and complex interactions between these cells and epidermal Langerhans' cells will have implications for VCA rejection and tolerance, and warrant further investigation in the allogeneic setting.read more
Citations
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Journal ArticleDOI
Acute rejection in vascularized composite allotransplantation.
Sebastian Fischer,Christine G. Lian,Maximilian Kueckelhaus,Terry B. Strom,Elazer R. Edelman,Rachel A. Clark,George F. Murphy,Anil Chandraker,Leonardo V. Riella,Stefan G. Tullius,Bohdan Pomahac +10 more
TL;DR: Acute rejection is higher in VCA than in any other organ in the field of transplantation, although most episodes are controlled by high-dose steroids and optimization of maintenance immunosuppression.
Journal ArticleDOI
Treg-inducing microparticles promote donor-specific tolerance in experimental vascularized composite allotransplantation
James D. Fisher,Stephen C. Balmert,Wensheng Zhang,Riccardo Schweizer,Jonas T. Schnider,Chiaki Komatsu,Liwei Dong,Vasil E. Erbas,Jignesh V. Unadkat,Ali Mubin Aral,Abhinav P. Acharya,Yalcin Kulahci,Heth R. Turnquist,Angus W. Thomson,Mario G. Solari,Vijay S. Gorantla,Steven R. Little +16 more
TL;DR: A synthetic, controlled-release microparticle system that aims to locally enrich naturally occurring, suppressive lymphocytes to prevent allograft rejection and promote tolerance may reduce, or even eliminate, the need for systemic immunosuppression in VCA or solid organ transplantation.
Journal ArticleDOI
Vascularized composite allografts and solid organ transplants: similarities and differences.
TL;DR: The review summarized the development in VCA over the past 12 months with references of and comparison with solid organ transplantation and novel targets for immunosuppression and immunomodulation including the application of mesenchymal stem cells for transplant tolerance.
Journal ArticleDOI
Exploring cell-based tolerance strategies for hand and face transplantation.
Madeline Fryer,Johanna Grahammer,Saami Khalifian,Georg J. Furtmüller,W. P. Andrew Lee,Giorgio Raimondi,Gerald Brandacher +6 more
TL;DR: Various cell-based approaches to tolerance induction currently under investigation in both clinical and pre-clinical models to alleviate the need for chronic immunosuppression are summarized.
Journal ArticleDOI
Vascularized composite allotransplant in the realm of regenerative plastic surgery.
TL;DR: Although VCA can restore form and function, it exposes the patient to the risks associated with lifelong immunosuppression, and VCA remains an immediate means of reconstructing otherwise unreconstructable defects.
References
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Journal ArticleDOI
HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression
Tatsuo Kawai,A. Benedict Cosimi,Thomas R. Spitzer,Nina Tolkoff-Rubin,Manikkam Suthanthiran,Susan L. Saidman,Juanita Shaffer,Frederic I. Preffer,Ruchuang Ding,Vijay K. Sharma,Jay A. Fishman,Bimalangshu R. Dey,Dicken S.C. Ko,Martin Hertl,Nelson Goes,Waichi Wong,Winfred W. Williams,Robert B. Colvin,Megan Sykes,David H. Sachs +19 more
TL;DR: Five patients with end-stage renal disease received combined bone marrow and kidney transplants from HLA single-haplotype mismatched living related donors, with the use of a nonmyeloablative preparative regimen, and it was possible to discontinue all immunosuppressive therapy 9 to 14 months after the transplantation.
Journal ArticleDOI
Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells
TL;DR: New developments in the understanding of the biology of LCs and other langerin+ DCs are described and the challenges that remain in identifying the role of different DC subsets in tissue immunity are discussed.
Journal ArticleDOI
Skin infection generates non-migratory memory CD8+ T(RM) cells providing global skin immunity.
Xiaodong Jiang,Rachael A. Clark,Luzheng Liu,Amy J. Wagers,Robert C. Fuhlbrigge,Thomas S. Kupper +5 more
TL;DR: It is shown in mice that localized vaccinia virus (VACV) skin infection generates long-lived non-recirculating CD8+ skin TRM cells that reside within the entire skin that are superior to circulating central memory T (TCM) cells at providing rapid long-term protection against cutaneous re-infection.
Journal Article
The behaviour and fate of skin autografts and skin homografts in rabbits: A report to the War Wounds Committee of the Medical Research Council
Journal Article
Immunologic functions of Ia-bearing epidermal Langerhans cells
TL;DR: The presence in the epidermis of Ia-bearing LC, capable of mediating the immunologic functions of I a-bearing macrophages, has important clinical implications with regard to the role of LC as sensitizing cells in both contact hypersensitivity and skin graft rejection.
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