Shaun A. Steigman, MD, Azra Ahmed, BS, Rabie M. Shanti, BS, Rocky S. Tuan, PhD, Clarissa Valim, MD, PhD, Dario O. Fauza, MD
Department of Surgery, Children’s Hospital; Boston, MA
PURPOSE OF STUDY
The treatment of severe congenital chest wall anomalies involving large sternal defects remains associated with high morbidity and mortality rates. We aimed at determining whether osseous grafts engineered from amniotic mesenchymal stem cells (AMSCs) could be employed in postnatal sternal repair.
Leporine AMSCs were transfected with green fluorescent protein (GFP), expanded, and seeded at identical densities onto electrospun poly(L-lactic) acid nanofibrous scaffolds (n=6). Constructs were maintained under hydrodynamic stimulation in an osteogenic medium, with confirmation of osteogenic differentiation after 3 months. Grafts were equally divided into two groups with respect to time in vitro, namely 3 or 8 months, when they were then surgically implanted to repair full thickness sternal defects spanning 2-3 intercostal spaces in allogeneic kits (n=6). Implants were submitted to multiple analyses before implantation and after 2 months in vivo. Statistical comparisons were by the signed-rank and Wilcoxon tests (P<.05).
SUMMARY OF RESULTS:
Chest roentgenograms showed defect closure in all animals, confirmed at necropsy. Graft density on micro-CT scans increased significantly in vivo, yet there were no differences in mineralization by extracellular calcium measurements pre- and post-implantation. There was a borderline significant increase in alkaline phosphatase activity in vivo. There were no differences between the two construct groups in any comparison. Histologically, grafts contained GFP-positive cells and few mononuclear infiltrates.
Engineered osseous grafts derived from amniotic mesenchymal stem cells are a viable alternative for sternal repair. Prolonged maintenance of the grafts in vitro does not enhance outcome. The amniotic fluid is a practical cell source for engineered chest wall reconstruction.