Regenerative Potential of Autologous Stem Cell Seeded, Polyphenol-Stabilized Acellular Valve Scaffolds in the Juvenile Sheep Model

OBJECTIVE: Our aim was to investigate the regenerative potential of xenogeneic acellular valve roots seeded with autologous stem cells. METHODS: First we prepared fully acellular porcine pulmonary roots and chemically... [ view full abstract ]

OBJECTIVE: Our aim was to investigate the regenerative potential of xenogeneic acellular valve roots seeded with autologous stem cells.
METHODS: First we prepared fully acellular porcine pulmonary roots and chemically stabilized them with penta-galloyl-glucose; non-stabilized scaffolds served as controls. We then isolated autologous adipose-derived stem cells (ASCs) from juvenile sheep, injected them within the acellular cusps and implanted them as valved conduits in the RVOT (n=6 per group). Unseeded valves served as controls.
RESULTS: Acellular roots showed excellent preservation of the matrix and hemodynamics. All animals had favorable post-operative evolution without complications. Short-term echographic follow-up showed that all implanted valves were functional. After about 4-5 weeks however, ASC-seeded valves were progressively covered with host fibrous tissue overgrowth resulting in right ventricular failure, while non-ASC-seeded valves were free of fibrous overgrowth. Cusps explanted from all implant groups showed complete absence of any interstitial cells (seeded or infiltrated) and lack of immune reactions, inflammation, calcification or thrombosis. Chemically stabilized, non-seeded valves were very durable and still functional even after 12 months in the sheep.
CONCLUSIONS: Stabilized acellular valve roots are excellent scaffolds with great potential to serve as alternatives to existing artificial valves and as scaffolds for regeneration. ASCs appear to be very vulnerable to valve-specific mechanical forces and their early in vivo demise might be related to excessive pannus formation in sheep. Ongoing studies focus on progressive mechanical conditioning of ASC-seeded valves in bioreactors for cell adaptation before implantation.
Funding: NIGMS #5P20GM103444-07, Harriet and Jerry Dempsey Bioengineering Professorship Award, CNCS-UEFISCDI #PNII-ID-PCCE-2011-2-0036.