Articles
Fetal tissue engineering: In utero tracheal augmentation in an ovine model

Presented at the 53rd Annual Meeting of the Section on Surgery of the American Academy of Pediatrics, San Francisco, California, October 19-21, 2001.
https://doi.org/10.1053/jpsu.2002.33829Get rights and content

Abstract

Background/Purpose: This study was aimed at comparing fetal tissue engineering with autologous free grafting in an ovine model of in utero tracheal repair. Methods: Chondrocytes were isolated from both elastic and hyaline cartilage specimens harvested from fetal lambs and expanded in vitro. Cells were seeded dynamically onto biodegradable scaffolds, which then were maintained in a rotating bioreactor for 6 to 8 weeks. Constructs subsequently were implanted into fetal tracheas (n = 15), in a heterologous fashion (group I). In group II, fetuses (n = 5) received autologous free grafts of elastic cartilage harvested from the ear as tracheal implants. In vivo specimens were harvested for histologic analysis at different time-points postimplantation. Results: In the 12 of 15 surviving fetuses of group I, all constructs were found to resemble normal hyaline cartilage, engraft well despite their heterologous origin, and display time-dependent epithelialization derived from the native trachea. All autologous free grafts were engrafted and epithelialized at birth, retaining histologic characteristics of elastic cartilage, but were more deformed than engineered constructs. Of the lambs allowed to reach term, 5 of 5 in the engineered group and 4 of 5 in the free graft group could breathe spontaneously. Conclusions: (1) Tissue-engineered cartilage, as well as autologous free grafts, can be implanted successfully into the fetal trachea, resulting in engraftment and function. (2) Engineered cartilage provides enhanced structural support after implantation into the fetal trachea when compared with free grafts. Prenatal tracheoplasty may prove useful for the treatment of severe congenital tracheal malformations. J Pediatr Surg 37:1000-1006. Copyright 2002, Elsevier Science (USA). All rights reserved.

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Materials and methods

The Harvard Medical School animal management program is sanctioned by the American Association for the Accreditation of Laboratory Animal Care (AAALAC, file # 000009) and meets National Institutes of Health standards as set forth in the Guide for the Care and Use of Laboratory Animals (National Research Council Publication, Revised 1996).

Results

Fetal survival rates were 80% (12 of 15) and 100% (5 of 5) for groups I and II, respectively (P =.54). Of those allowed to reach term, postnatal survival rates were 100% (5 of 5) in group I and 90% (4 of 5) in group II (P = 1.0). Similarly, of the lambs permitted to reach term, 5 of 5 in the engineered group (group I) and 4 of 5 in the free graft group (group II) were able to breathe spontaneously at birth without mechanical ventilation (P = 1.0). Stridor was present in 3 of 5 animals in group

Discussion

Given the current limitations of fetal intervention, the use of fetal tissue engineering techniques, with or without in utero repair, can only be justified for life-threatening anomalies. Long-segment tracheal atresia and stenosis meet this criterion. Currently, mortality rates are high, reaching up to 77% for long-segment tracheal stenosis and nearly 100% for long-length tracheal atresia.6, 7, 8 To date, the optimal method and material for tracheal grafting and replacement have yet to be

Acknowledgements

The authors thank Jeffrey Petitt for his excellence in laboratory assistance.

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Address reprint requests to Dario O. Fauza, MD, Children's Hospital, 300 Longwood Ave, Fegan 3, Boston, MA 02115.

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