Exploring cell-based tolerance strategies for hand and face transplantation.
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.
a 1 Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Ross Research Building Room 749, 720 Rutland Avenue, Baltimore, MD, 21205, USA.
Madeline
M
Fryer
b 2 Department of Visceral Transplant and Thoracic Surgery, Center of Operative Medicine, Innsbruck Medical University, Innsbruck, Austria.
Johanna
J
Grahammer
a 1 Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Ross Research Building Room 749, 720 Rutland Avenue, Baltimore, MD, 21205, USA.
Saami
S
Khalifian
a 1 Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Ross Research Building Room 749, 720 Rutland Avenue, Baltimore, MD, 21205, USA.
Georg J
GJ
Furtmüller
a 1 Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Ross Research Building Room 749, 720 Rutland Avenue, Baltimore, MD, 21205, USA.
W P Andrew
WP
Lee
a 1 Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Ross Research Building Room 749, 720 Rutland Avenue, Baltimore, MD, 21205, USA.
Giorgio
G
Raimondi
a 1 Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Ross Research Building Room 749, 720 Rutland Avenue, Baltimore, MD, 21205, USA.
Gerald
G
Brandacher
D064591:Allografts; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D054445:Facial Transplantation / Q000379:methods*; D063987:Hand Transplantation / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D023001:Transplantation Tolerance
mesenchymal stem cell; mixed chimerism; regulatory B cell; regulatory T cell; regulatory macrophage; tolerance; tolerogenic dendritic cell; vascularized composite allotransplantation