Fetal tracheal reconstruction with cartilaginous grafts engineered from mesenchymal amniocytes

Abstract

Background/purpose: This study was aimed at determining whether cartilaginous grafts engineered from mesenchymal cells normally present in the amniotic fluid could be used in fetal tracheal repair.

Methods: Ovine mesenchymal amniocytes were expanded in culture, labeled with green fluorescent protein, and seeded onto biodegradable scaffold tubes maintained in chondrogenic medium. After chondrogenic differentiation of the constructs was confirmed, they were used to repair either partial or full circumferential tracheal defects in allogeneic fetal lambs (n = 7). Newborns were evaluated for signs of airway compromise. Implants were harvested over a 10-day period postnatally for multiple analyses.

Results: All 5 lambs that survived to term were able to breathe spontaneously at birth, 4 (80%) of them without stridor. However, variable degrees of stridor developed over time in all but one animal. Mild-to-moderate tracheal stenosis was present in all specimens. Histologically, grafts contained green fluorescent protein-positive cells, were lined with pseudostratified columnar epithelium, and remodeled into a predominantly fibrous cartilage pattern. Implants showed no significant changes in glycosaminoglycans, collagen, and elastin content at harvest.

Conclusions: Engineered cartilaginous grafts derived from mesenchymal amniocytes may become a viable alternative for tracheal repair. The amniotic fluid can be a practical cell source for engineered tracheal reconstruction.