AAP Paper
Sternal repair with bone grafts engineered from amniotic mesenchymal stem cells,☆☆

https://doi.org/10.1016/j.jpedsurg.2009.02.038Get rights and content

Abstract

Purpose

We aimed at determining whether osseous grafts engineered from amniotic mesenchymal stem cells (aMSCs) could be used in postnatal sternal repair.

Methods

Leporine aMSCs were isolated, identified, transfected with green fluorescent protein (GFP), expanded, and seeded onto biodegradable electrospun nanofibrous scaffolds (n = 6). Constructs were dynamically maintained in an osteogenic medium and equally divided into 2 groups with respect to time in vitro as follows: 14.6 or 33.9 weeks. They were then used to repair full-thickness sternal defects spanning 2 to 3 intercostal spaces in allogeneic kits (n = 6). Grafts were submitted to multiple analyses 2 months thereafter.

Results

Chest roentgenograms showed defect closure in all animals, confirmed at necropsy. Graft density as assessed by microcomputed tomographic scans increased significantly in vivo, yet there were no differences in mineralization by extracellular calcium measurements preimplantation and postimplantation. There was a borderline increase in alkaline phosphatase activity in vivo, suggesting ongoing graft remodeling. Histologically, implants contained GFP-positive cells and few mononuclear infiltrates. There were no differences between the 2 construct groups in any comparison.

Conclusions

Engineered osseous grafts derived from amniotic mesenchymal stem cells may become a viable alternative for sternal repair. The amniotic fluid can be a practical cell source for engineered chest wall reconstruction.

Section snippets

Materials and methods

This study was approved by the Institutional Animal Care and Use Committee of Children's Hospital Boston under protocol no. A05-12-104.

Results

There were no postoperative complications or mortality after the chest wall reconstructions. Chest roentgenograms performed at 2 months postimplantation showed radiodense material overlying the repaired defect in all rabbits (Fig. 2). Necropsy similarly demonstrated complete closure of the defect in all animals, with the constructs still distinctly visible amid native tissue.

Discussion

The translational implication of the concept explored herein is self-explanatory. Once the diagnosis of a major congenital chest wall anomaly is made through fetal imaging, an autologous osseous graft would be engineered in parallel to gestation, so that the affected neonate could benefit from its availability immediately after birth. Given that a diagnostic amniocentesis is routinely indicated in the setting of any major congenital structural anomaly, combined with the anticipated autologous

Acknowledgments

The authors thank Dr Arthur Nedder and Mr Mark Kelly for their exemplary veterinary care.

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SAS was supported by the Joshua Ryan Rappaport Fellowship of the Department of Surgery, Children's Hospital Boston (Mass).

☆☆

Presented at the 60th Annual Meeting of the Section on Surgery, American Academy of Pediatrics, Boston, Mass, October 10-12, 2008.

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