Split tolerance in a murine model of heterotopic En bloc chest wall transplantation

Byoung Chol Oh, Georg J. Furtmüller, Veronika Malek, Madeline L. Fryer, Cory Brayton, Piotr Walczak, Miroslav Janowsky, Gerald Brandacher, Amir Dorafshar

Research output: Contribution to journalArticle

Abstract

Background: Congenital and acquired chest wall deformities represent a significant challenge to functional reconstruction and may impact feasibility of heart transplantation for patients with end-stage organ failure. In the recent past, the concept of replacing like-with-like tissue by using vascularized composite allografts (VCA) has been enthusiastically employed for reconstruction of complex tissue defects. Methods: In this study, we introduce a novel murine model for en bloc chest wall, heart, and thymus transplantation and thereby the use of complex tissue allografts for reconstruction of both chest wall defects and also end-stage organ failure. Additionally, this model allows us to study the features of combined vascularized bone marrow (VBM), thymus, and heart transplantation on allograft survival and function. Heterotopic chest wall, thymus, and heart transplants were performed in untreated syngeneic and allogeneic combinations and in allogeneic combinations treated with costimulation blockade (CTLA4-Ig and MR-1). Results: Indefinite (ie, 150 d, N = 3) graft survival was observed in syngeneic controls. In untreated recipients of allogeneic grafts, the skin component was rejected after 10 (±1) days, whereas rejection of the heart occurred after 13 (± 1) days (N = 3). Costimulation blockade treatment prolonged survival of the heart and chest wall component (130 d, N = 3) as well as the VBM niche as evidenced by donor-specific chimerism (average: 2.35 ± 1.44%), whereas interestingly, the skin component was rejected after 13 (±1) days. Conclusion: Thus, this novel microsurgical model of VCA combined with solid organ transplantation is technically feasible and results in split tolerance when treated with costimulatory blockade.

Original languageEnglish (US)
Article numbere1595
JournalPlastic and Reconstructive Surgery - Global Open
Volume5
Issue number12
DOIs
StatePublished - Jan 1 2017

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Thoracic Wall
Transplantation
Composite Tissue Allografts
Heart Transplantation
Thymus Gland
Allografts
Transplants
Skin
Chimerism
Organ Transplantation
Graft Survival
Bone Marrow Transplantation
Bone Marrow
Tissue Donors

ASJC Scopus subject areas

  • Surgery

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Split tolerance in a murine model of heterotopic En bloc chest wall transplantation. / Oh, Byoung Chol; Furtmüller, Georg J.; Malek, Veronika; Fryer, Madeline L.; Brayton, Cory; Walczak, Piotr; Janowsky, Miroslav; Brandacher, Gerald; Dorafshar, Amir.

In: Plastic and Reconstructive Surgery - Global Open, Vol. 5, No. 12, e1595, 01.01.2017.

Research output: Contribution to journalArticle

Oh, Byoung Chol ; Furtmüller, Georg J. ; Malek, Veronika ; Fryer, Madeline L. ; Brayton, Cory ; Walczak, Piotr ; Janowsky, Miroslav ; Brandacher, Gerald ; Dorafshar, Amir. / Split tolerance in a murine model of heterotopic En bloc chest wall transplantation. In: Plastic and Reconstructive Surgery - Global Open. 2017 ; Vol. 5, No. 12.
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