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Updated: Feb 12, 2026
A Novel Microsurgical Model for Heterotopic, En Bloc Chest Wall, Thymus, and Heart Transplantation in Mice
Published on: January 23, 2016
Split Tolerance in a Murine Model of Heterotopic En Bloc Chest Wall Transplantation
Byoungchol Oh1, Georg J Furtmüller1, Veronika Malek1
1Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, Md.; Ruprecht-Karls University Heidelberg Medical Faculty, Heidelberg, Germany; Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Md.; and Radiology and Radiological Science-Magnetic Resonance Research, Institute for Cell Engineering, Kennedy Krieger Institute's F.M. Kirby Research Center, Baltimore, Md.
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.
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