Tracheal Replacement by Allogenic Aorta in the Pig: Conclusion

Early results showing no evidence of ischemia or acute rejection were encouraging, despite the absence of blood or tissue compatibility, and without any IT. As in sheep, major inflammatory reactions in the graft were observed within the first 3 months. Subsequent fate of AA followed a similar pattern as in sheep, but over a longer period of time. Evidence of AA progressively vanished, but, microscopically, elastic fibers retaining basic morphologic features could still be identified up to the 11th month. Development of a typical longitudinal posterior membrane could be seen at 10 months, together with immature cartilage and disorganized elastic fibers. The cartilaginous deposits that were seen did not form a continuous tubular structure, but rather were distributed in islets with a trend toward transverse orientation. These cartilaginous formations also showed discernible bony trabeculae. Although only a few animals could be studied long enough to show cartilage formation, our results lend support to the original experiments of Martinod et al and Seguin et al, and expand them to a new level by increasing the extent of tracheal resection, thus reducing or eliminating the possibility that neocartilage seen in the neotracheal conduit arises from the edges of native trachea pulled into the graft by scar contraction.
Transplantation of female aorta into male recipients was intentional, so as to enable later assessment of the graft for the presence of the SRY gene. Positive SRY gene detection, particularly at the level of the newly formed cartilage, serves as evidence of engraftment of cells derived from the male recipient. We thus hypothesize that the graft was colonized by recipient multipotent mesenchymal stem cells (MSCs) that when triggered by environmental cues differentiated into chondrocytes.
Cartilaginous differentiation of MSCs in the arterial walls is a well-documented phenomenon. MSCs are multipotent human leukocyte antigen class II negative cells able to differentiate along multiple lineages, giving rise to cartilage, bone, fat, muscle, and vascular tissue. MSCs serve as universal repair cells and are able to enter the circulation and engraft other tissues, including the arterial wall. Environmental cues, driving the commitment of MSCs to a particular differentiation pathway, are under investigation.
This study confirms that fresh AA, when replacing long tracheal segments in the pig, transforms into a conduit containing the major tracheal components. Questions remain concerning the exact mechanisms of this process. These components are still relatively immature, and the newly formed respiratory conduit does not as yet replicate the form and function of the native trachea. Further research in the field is recommended.

This entry was posted in Allogenic Aorta and tagged airway, lung cancer, transplants.