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. 2024 Dec 30;14(1):31930.
doi: 10.1038/s41598-024-83378-4.

A novel technique for heart-thymus en bloc transplantation in nonhuman primates

James T Nawalaniec  1   2 , Samantha M Landino  1   2 , Jane M O  2 , Cynthia L Miller  1   2 , Abbas Dehnadi  2 , Isabel Hanekamp  2 , Jayne Marie Muoio  2 , Casey Winter  2 , Nicole Hays  2   3 , James S Allan #  2   4 , Joren C Madsen #  5   6
Affiliations

A novel technique for heart-thymus en bloc transplantation in nonhuman primates

James T Nawalaniec et al. Sci Rep. .

Abstract

The thymus is a rich source of regulatory T cells and plays a role in self-tolerance. Therefore, transplantation of a vascularized donor thymus may facilitate the induction of tolerance in recipients of a cotransplanted heart allograft. To investigate this hypothesis, we developed a new technique to procure the heart and thymus en bloc from juvenile donors and transplant the composite allograft into thymectomized recipients. Thymic function was monitored by serial biopsy and flow cytometry of peripheral blood. Heart-thymus en bloc transplantation resulted in immediate revascularization of the heart and donor thymus with maintenance of normal thymic architecture, even in biopsies taken months after transplantation. Heart-thymus en bloc transplantation requires minimal modification to current heart procurement techniques. Here, we describe the details of the preparation, procurement, transplantation, and postoperative monitoring for this model, with the intention that this technique could be implemented by other investigators to study the effects of heart and thymus cotransplantation. This method could ultimately offer a new approach to tolerance induction in children.

Keywords: Heart transplant; Pediatric heart transplant; Regulatory T cells; Thymus transplant; Tolerance.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The bilateral carotid arteries and internal jugular veins have been encircled with proximal and distal silk ties. The bilateral subclavian veins are encircled, but still intact in this image. The internal mammary arteries (IMAs) are intact and dissected from the chest wall, lying with the thymus.
Fig. 2
Fig. 2
The composite allograft on the back table. The posterior surface of the heart is visible, with the thymus and bilateral IMAs reflected superiorly, so that the anterior surface is displayed. The aorta remnant is visible.
Fig. 3
Fig. 3
The recipient inferior vena cava (IVC) and aorta have been controlled together with a single Satinsky clamp. The pulmonary artery (PA) of the donor heart has been anastomosed to the recipient inferior vena cava. The aortic anastomosis has not yet started.
Fig. 4
Fig. 4
Diagram of the donor heart and thymus composite allograft after completing the aortic and pulmonary artery anastomoses. The thymus has been rotated cephalad to demonstrate the vascular anatomy of the allograft. PA: pulmonary artery. IVC: inferior vena cava. Venous drainage of the thymus by the IMVs is not shown.
Fig. 5
Fig. 5
Final position of the composite allograft with the thymus in the natural position anterior to the heart. The arch anatomy is obscured by the pericardial and thymic tissue.
Fig. 6
Fig. 6
Example of transabdominal ultrasound showing the right and left ventricles of the transplanted allograft. The ultrasound can be used to monitor contractility and ventricular thickness, as surrogate markers for rejection.
Fig. 7
Fig. 7
Wedge biopsy of transplanted thymus on low power (left) and high power (right). A Hassan’s corpuscle is outlined in the black box. This sample was taken from M5923, 132 days after transplant.
Fig. 8
Fig. 8
Flow cytometry gating strategy for staining peripheral blood for RTEs.
See this image and copyright information in PMC

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