Abstract 11023: Development of a Biomimetic Tri-Leaflet Valved Tube Seeded with Wharton's Jelly-Derived Mesenchymal Stem Cells for Replacement of the Right Ventricular Outflow Tract
INTRODUCTION: Materials currently used for replacement of the Right Ventricular Outflow Tract (RVOT) in congenital heart diseases yield suboptimal results without growth potential, and may require multiple reoperations. HYPOTHESIS: We tried to improve outcomes by developing a tri-leaflet valved tube made of a bioresorbable polymer, seeded with autologous mesenchymal stem cells (MSC) derived from the Wharton’s jelly of the cord.
METHODS: The tube and the valve were made of woven poly-L-lactic acid (PLLA) and PLLA+polyester respectively. A computer-assisted modeling defined the geometry of the tri-leaflet valve and its insertion modalities within the conduit. In vitro mechanical tests evaluated the permeability and strength of the tube and the competence, fatigue, and anisotropy of the valve. Autologous Wharton’s jelly-derived MSC were seeded in static (3,5x106 MSC /cm² for 4 days) and then dynamic conditions in a customized bioreactor. The concept was then tested in vivo by using initially resorbable MSC-seeded patches implanted into the RVOT of 6 3-month-old lambs and evaluated by MRI and immunohistochemistry up to 8 months after surgery.
RESULTS: Tubes (n=11; diameter: 18mm; thickness: 350µm) displayed an excellent burst strength performance (mean: 303±43N). MSC could reproducibly be grown from cord explants and expressed the expected markers (CD29, 49a, 49f). Optimizing the duration and pressure and flow conditions during the dynamic maturation phase in bioreactor improved both the biological (cell density and viability, seeding homogeneity) and mechanical (burst strength, water permeability) characteristics of the tube. In vivo implantation of resorbable seeded patches revealed the complete degradation of the polymeric scaffold which was colonized by host cells with histological evidence for an endothelial lining and an extracellular matrix close to that of the native pulmonary artery. CONCLUSIONS: These proof-of-concept experiments support the interest of a completely bioresorbable polymeric valved device seeded with autologous Wharton’s jelly-derived MSC. This non-invasive source of autologous stem cells, available at birth, could be used to treat a neonate with a prenatal diagnosis of congenital heart defect.
- Tissue engineering
- Regenerative medicine stem cells
- Stem/progenitor cells
- Congenital heart surgery
- Pulmonary artery
- © 2012 by American Heart Association, Inc.