APSA Paper
Diaphragmatic repair through fetal tissue engineering: a comparison between mesenchymal amniocyte– and myoblast-based constructs

https://doi.org/10.1016/j.jpedsurg.2005.10.011Get rights and content

Abstract

Purpose

We have previously shown that fetal tissue engineering is a preferred alternative to diaphragmatic repair in a large animal model. This study was aimed at comparing diaphragmatic constructs seeded with mesenchymal amniocytes and fetal myoblasts in this model.

Methods

Neonatal lambs (n = 14) underwent repair of an experimental diaphragmatic defect with identical scaffolds, either seeded with labeled autologous cells (mesenchymal amniocytes in group 1 and fetal myoblasts in group 2) or as an acellular graft (group 3). At 1 to 12 months postoperatively, implants were harvested for multiple analyses.

Results

Repair failure (reherniation or eventration) was significantly higher in group 3 than in groups 1 and 2, with no difference between groups 1 and 2. Seeded fetal myoblasts quickly lost their myogenic phenotype in vivo. All grafts contained cells with a fibroblastic-myofibroblastic profile. Elastin concentrations and both modular and ultimate tensile strengths were significantly higher in group 1 than in groups 2 and 3. There were no differences in glycosaminoglycans and type I collagen levels among the groups.

Conclusions

Diaphragmatic repair with a mesenchymal amniocyte–based engineered tendon leads to improved structural outcomes when compared with equivalent fetal myoblast–based and acellular grafts. The amniotic fluid is a preferred cell source for tissue-engineered diaphragmatic reconstruction.

Section snippets

Materials and methods

This study was approved by the Harvard Medical School Standing Committee on Animals under protocol no. 03354. For groups 1 and 3, as defined below, this study consisted of post hoc analyses of previously reported animals/grafts [2].

Results

Graft failure was observed in all groups, albeit significantly more frequent in group 3 (5/5, 100%) than in groups 1 and 2 combined (2/9, 22.9%; Fig. 1). There was no statistical difference between groups 1 (1/4, 25%) and 2 (1/5, 20%).

Labeled cells were found in all grafts in groups 1 and 2. However, group 1 grafts appeared to have increased cellularity, as well as higher capillary density by CD31 staining, when compared with groups 2 and 3, although this could not be quantified. As early as 1

Discussion

Over the past 2 decades, CDH mortality rates have decreased dramatically [10], [11]. This increased survival has led to previously unrecognized morbidities, such as recurrence of the diaphragmatic hernia, which is known to be more prevalent after prosthetic repair [12], [13], [14], [15]. Hernia recurrence is believed to stem from normal growth, which leads to traction and eventual detachment of the prosthesis [16]. According to the Congenital Diaphragmatic Hernia Study Group, the most infants

Acknowledgments

The authors thank Ms Tonora Archibald (Department of Pathology, Children's Hospital Boston) for her outstanding histology processing and Mr Jeffrey Pettit (Division of Surgery, Harvard Medical School) for his excellence in surgical laboratory assistance.

Cited by (105)

  • The Future of Fetal Surgery

    2021, Obstetrics and Gynecology Clinics of North America
  • Fetal Tissue

    2019, Encyclopedia of Tissue Engineering and Regenerative Medicine: Volumes 1-3
  • Mesenchymal Stem Cells From Amniotic Fluid for Treating Congenital and Other Diseases

    2019, Encyclopedia of Tissue Engineering and Regenerative Medicine: Volumes 1-3
  • Scaffolds for reconstruction of the diaphragm

    2019, Handbook of Tissue Engineering Scaffolds: Volume Two
View all citing articles on Scopus

Presented at the 36th Annual Meeting of the American Pediatric Surgical Association, Phoenix, AZ, May 29-June 1, 2005.

S.M.K. was supported by grants from the National Institutes of Health National Research Service Award DK065406-02 and the V.H. Kazanjian Surgical Research Fellowship of the Massachusetts General Hospital.

View full text