Boston - American Association for Thoracic Surgery

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89 TH ANNUAL MEETING MAY 9–MAY 13, 2009BOSTON, MASSACHUSETTSSUNDAY AFTERNOONMAY 10, 20093:00 p.m. C. WALTON LILLEHEI RESIDENT FORUM SESSIONRoom 311, Hynes Convention Center(7 minutes presentation, 8 minutes discussion)Moderators: Gus J. Vlahakes, Ara A. VaporciyanL1. In Vivo Structure and Function of Engineered PulmonaryValvesDanielle Gottlieb 1 , Kunal Tandon 1 , Sitaram Emani 1 , Elena Aikawa 2 ,David W. Brown 1 , Andrew J. Powell 1 , Arthur Nedder 1 , Michael S. Sacks 3 ,John E. Mayer 1*1. Children’s Hospital Boston and Harvard Medical School, Boston, MA, USA;2. Massachusetts General Hospital and Harvard Medical School, Boston, MA,USA; 3. University of Pittsburgh, Pittsburgh, PA, USAol, Boston, MA, USA; 3 University of Pittsburgh, Pittsburgh, PA, USAOBJECTIVE: Clinical translation of engineered heart valves requires valve competencyin the short and long-term. Early studies of engineered heart valves showedpromise, though lacked complete definition of valve function. Building on priorexperiments, we sought to define a time course of the in vivo changes in structureand function of autologous engineered pulmonary valves (PV).METHODS: Mesenchymal stem cells (MSCs) were isolated from the mononuclearfraction of bone marrow collected from nine neonatal lambs. Cells were characterized,expanded, and seeded onto a 3D heart valve scaffold composed ofpolyglycolic acid (PGA) and poly-L-lactic acid (PLLA). After 4 weeks of culture,sheep underwent autologous PV replacement on cardiopulmonary bypass. Valvefunction was evaluated by epicardial echocardiography at implantation, by MRI atthe experimental midpoint, and by epicardial echocardiography at explant of thevalve at either 6 weeks (n = 3), 12 weeks (n = 3), or 20 weeks (n = 3) post-operatively.Conduit size was measured at the time of implantation and at explantation.Explanted tissues were processed for histology.RESULTS: All nine animals survived and were clinically well until valve explant.Evaluation of immediate valve function demonstrated a mean transvalvar gradientof 15.2 mmHg (range 10–20 mmHg), and mean pulmonary regurgitation (PR)score of 0.58 (trivial = 0, mild = 1, moderate = 2, severe = 3). Valve functionremained adequate at 3 and 6 weeks (PR fraction ≤20%), though leaflets appearedincreasingly immobile, resulting in an increasing regurgitant fraction over time.* AATS Member54
AMERICAN ASSOCIATION FOR THORACIC SURGERYSUNDAYAfternoonFigure. Representative short axis epicardialechocardiographic view of an engineeredpulmonary valved conduit at the time ofimplantation.Conduit diameter was unchanged over 20 weeks. Engineered leaflets and conduitwalls underwent dynamic remodeling over the time course, as evidenced by cellproliferation (Ki67), inflammation (CD45), remodeling enzyme expression (MMP-1, -2, -9, -13) and microvessel formation (CD31) at the early stages, and progressiveGAG (versican) and collagen organization (anti-collagen; Masson trichrome) andcomplete endothelization in long-term explants.CONCLUSION: In the largest in vivo series published, we demonstrate reproduciblefabrication and implantation of autologous engineered pulmonary valves whichfunction well at implantation. In vivo valves undergo structural and functionalremodeling resulting in the onset of pulmonary regurgitation after 6 post-operativeweeks. Tissue engineered conduits stayed stable in size after 5 months with no evidenceof conduit stenosis or aneurysm formation.55
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AATS FUTURE MEETINGSMay 1-5, 2010Me
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Boston - American Association for Thoracic Surgery

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