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Background: This study aimed at determining whether a complete airway construct engineered from autologous amniotic mesenchymal stem cells (aMCS) and a xenologous decellularized airway scaffold could be employed as a segmental tracheal substitute.
Methods: Fetal lambs (n=13) with full segmental tracheal defects were divided into two groups, based on how the defect was repaired. One group (acellular, n=6) received a size-matched decellularized leporine tracheal segment. The other group (engineered, n=7) received an identical graft, but seeded with autologous, labeled aMSCs maintained under hydrodynamic stimulation in a chondrogenic medium. Normal delivery was allowed, followed by euthanasia within the first week for multiple analyses.
Results: Eleven lambs survived to term, 10 of which could breathe spontaneously at birth. Engineered grafts showed a significant increase in diameter in vivo (p=0.04), with no difference detected in the acellular group (p=0.62), though variable stenosis was present in all implants. All survivors with engineered constructs exhibited full epithelialization of the graft, compared to none of those treated with acellular grafts (p=0.002). Engineered grafts had a significantly greater degree of increase in elastin levels after implantation than the acellular grafts (p=0.04). No such differences were noted in collagen and glycosaminoglycan contents. Histologically, labeled cells were detected in engineered grafts, which displayed a pseudostratified columnar epithelium.
Conclusion: Grafts engineered from amniotic mesenchymal stem cells and decellularized airway undergo enhanced remodeling and epithelialization patterns in vivo when compared with an equivalent acellular airway implant. Amniotic mesenchymal stem cell-engineered airway may become a viable, practical alternative for perinatal airway repair.