Transplantation of the cryopreserved tracheal allograft in growing rabbits: effect of immunosuppressant

Abstract

Transplantation of a cryopreserved tracheal allograft is considered to be a useful strategy in treating congenital tracheal stenosis. Recent reports of tracheal transplant experiments have shown that the antigenicity of the trachea is decreased by cryopreservation, making transplantation of the trachea possible. However, we reported that cryopreserved tracheal allografts exhibited favorable patency, but no significant growth in an animal model. In this study, we hypothesize that an immune reaction may play a role in the failure of an allograft's growth. Each allograft was harvested from 90- to 120-day-old Japanese rabbits, immersed in preservation solution, stored in a programmable freezer until it reached -80 C, and then kept for 1 month. Orthotopic tracheal transplantation of four tracheal rings in an end-to-end fashion was performed in age-matched young rabbits. Ten recipients were classified into three groups: a group provided with tacrolimus (FK-506) as an immunosuppressant (n = 6), a group receiving a graft irradiated before transplantation (n = 2), and a control group (n = 2). All grafts were evaluated 4-8 weeks after transplantation (tacrolimus group: 3-13 weeks). Body weight gain of the tacrolimus group was less than that of the other two groups. All grafts were well incorporated with the recipients macroscopically, but the grafts showed no growth in diameter. Microscopic examination showed inflammation in the tacrolimus and control groups temporarily. The irradiated allografts had marked fibrosis in the subepithelium. Although calcification of the tracheal cartilage was present in all transplanted allografts, the difference between groups was not significant. Patency of the cryopreserved tracheal allografts was favorable but no growth occurred even with an immunosuppressant. Further studies are required to address the growth of the tracheal allograft.

Effects of cryopreservation on tracheal allograft antigenicity in dogs

“…Based on a considerable body of evidence, it is the antigenicity of tracheal allografts that mandates intervention after transplantation to control the immune response (14,19). Indeed, when Yokomise and colleagues performed fresh tracheal transplantation in five mongrel dogs (20), without immunosuppressive treatment, all of the animals died from severe tracheal stenosis (i.e., rejection) within 1 month.…”

“…The longest observation period at time of publication was 293 days. A variety of similar experiments in rats, rabbits, dogs, and even nonhuman primates have since ensued (13)(14)(15)(16).…”

Ultrastructural Changes in Cryopreserved Tracheal Grafts of Sprague-Dawley Rats

“…Afterward, many experimental studies investigated the usefulness of cryopreserved tracheal grafts using different animal models. [17][18][19] However, cryopreservation not only reduces the antigenicity of tracheal grafts but also damages tracheal cartilage. It is necessary to investigate the alteration of tracheal grafts during cryopreservation.…”

Cryopreservation of the tracheal grafts

“…76 On the other hand, Hisamatsu and colleagues studied growth of cryopreserved tracheal allotransplant using rabbits for the treatment of congenital tracheal stenosis, and demonstrated that patency of the cryopreserved tracheal allografts was favorable, but no growth occurred even with the use of an immunosuppressant. 77 This issue will also be the subject of future investigated.…”