A Novel Microsurgical Model for Heterotopic, En Bloc Chest Wall, Thymus, and Heart Transplantation in Mice

Abstract

Exploration of novel strategies in organ transplantation to prolong allograft survival and minimizing the need for long-term maintenance immunosuppression must be pursued. Employing vascularized bone marrow transplantation and co-transplantation of the thymus have shown promise in this regard in various animal models. Vascularized bone marrow transplantation allows for the uninterrupted transfer of donor bone marrow cells within the preserved donor microenvironment, and the incorporation of thymus tissue with vascularized bone marrow transplantation has shown to increase T-cell chimerism ultimately playing a supportive role in the induction of immune regulation. The combination of solid organ and vascularized composite allotransplantation can uniquely combine these strategies in the form of a novel transplant model. Murine models serve as an excellent paradigm to explore the mechanisms of acute and chronic rejection, chimerism, and tolerance induction, thus providing the foundation to propagate superior allograft survival strategies for larger animal models and future clinical application. Herein, we developed a novel heterotopic en bloc chest wall, thymus, and heart transplant model in mice using a cervical non-suture cuff technique. The experience in syngeneic and allogeneic transplant settings is described for future broader immunological investigations via an instructional manuscript and video supplement.

Engineering Programmed Death Ligand-1/Cytotoxic T-Lymphocyte-Associated Antigen-4 Dual-Targeting Nanovesicles for Immunosuppressive Therapy in Transplantation

“…In brief, the model of heterotopic heart transplantation in mouse necks was based on the cuff-technique method. 36 Preparation of the recipient mice: The external jugular vein and jugular artery of the recipient mice were dissociated, ligated at the distal end of the vein, and then clipped at the proximal end of the vein with a blood vessel clamp. Next, the external jugular vein and jugular artery were passed through the venous cannula, turned out the intima of the vessel, and fixed with an 8-0 suture.…”

“…To carry out heart transplantation, hearts from male BALB/c mice as donors were transplanted into the necks of 8-week-old male C57BL/6 mice (weight >22 g), while the transplanted hearts were monitored by the palpitation of the grafts. In brief, the model of heterotopic heart transplantation in mouse necks was based on the cuff-technique method . Preparation of the recipient mice: The external jugular vein and jugular artery of the recipient mice were dissociated, ligated at the distal end of the vein, and then clipped at the proximal end of the vein with a blood vessel clamp.…”

Protective action of bone marrow mesenchymal stem cells in immune tolerance of allogeneic heart transplantation by regulating CD45RB+ dendritic cells

“…Wistar rats were treated as donors and SD rats as recipients, based on which rat models were established with improved cuff technique for cervical heart transplantation . When the SD rats were anesthetized, the external jugular veins were isolated.…”