Boston - American Association for Thoracic Surgery

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89 TH ANNUAL MEETING MAY 9–MAY 13, 2009BOSTON, MASSACHUSETTSF2. Repair of the Right Ventricular Outflow Tract by a MesenchymalStem Cell-Seeded Bioabsorbable Valved Patch: Medium-TermFollow-Up in a Growing Lamb ModelDavid Kalfa, 1 Alain Bel, 2 Annabel Chen-Tournoux, 1 Philippe Rochereau, 1Cyrielle Coz, 1 Valérie Bellamy, 1 Elie Mousseaux, 3 Patrick Bruneval, 4Jérôme Larghero, 5 Philippe Menasché 1*1. INSERM U633, Paris, France; 2. Hôpital Européen Georges Pompidou,Department of Cardiovascular <strong>Surgery</strong>; University Paris Descartes, Paris, France;3. Hôpital Européen Georges Pompidou, Department of Radiology, UniversityParis Descartes, Paris, France; 4. Hôpital Européen Georges Pompidou, Departmentof Pathology, University Paris Descartes, Paris, France; 5. Hôpital Saint-Louis,Laboratory of Cell Therapy; University Paris Diderot, Paris, FranceInvited Discussant: Bret MettlerOBJECTIVE: A major issue in congenital heart surgery is the lack of viable rightventricular outflow tract (RVOT) replacement materials with a growth potentialavoiding reoperations. We assessed the feasibility of restoring a living, autologousRVOT in a growing lamb model, using autologous mesenchymal stem cells(MSCs) seeded on a polydioxanone (PDO) bioabsorbable valved patch.METHODS: Autologous peripheral blood-derived MSCs were phenotypicallycharacterized, labeled with quantum dots, seeded onto monocusp-fitted PDO bioabsorbablepatches and cultured <strong>for</strong> 6 days. These patches were implanted in atransannular position into the RVOT of 6 growing lambs (group I), with 1, 4, or8 months of follow-up. Unseeded PDO valved patches (group II, n = 2) and autologouspericardial patches fitted with a polytetrafluoroethylene monocusp (group III,n = 2) were used as controls. Morphological and functional data on the RVOTwere evaluated by echocardiography (US) and MRI. Explanted specimens wereassessed by gross examination, histology, immunohistochemistry and calciumcontent assays.RESULTS: US and MRI did not show stenosis (peak gradient: 3.2 ± 1.2 mmHg,mean ± SD) or aneurysm (pulmonary annular dilation: +18% ± 9% (16 mm →18,9 mm) in group I. Gross examination and biochemical assays of cell-seededpatches demonstrated a better tissue growing, less retraction, less fibrosis and lesscalcifications compared to the standard-of-care group III (0.08% ± 0.03% Ca2+ vs.3.6% ± 0.65%). Histology in group I revealed complete biodegradation of the PDOscaffold, a viable, layered, endothelialized tissue (Figure) and an extracellularmatrix (with elastic fibers) comparable to that native ovine tissue. The neo-tissuethat reconstituted the RVOT exhibited environment-dependent differentiation patterns:the proximal portion of the patch harbored cells expressing cardiac myosinwhereas its distal segment harbored α-smooth muscle actin (SMA)-expressingmyofibroblasts. Only group I patches demonstrated cells with an endothelialphenotype (vW factor) on the luminal surface. Quantum dots were found in vWForα-SMA-positive cells at 1 month, thereby suggesting that at least some of themwere donor-derived.* AATS Member124
AMERICAN ASSOCIATION FOR THORACIC SURGERYHematoxylin-Eosin staining of the vascular (pulmonaryartery) segments of a tissue-engineered patch (group I,panel A) and a control pericardial patch (group III,panel B) after 4 months. Panel A: Polydioxanone iscompletely degraded, and a viable layered tissue similarto that of the native pulmonary artery (PA) is restored(with a neo-intima, a neo-media and a neo-adventitia).Panel B: the pericardial patch is calcified, degeneratedand surrounded by a dense inflammatory tissue.Magnification: ×5.TUESDAYMorningCONCLUSION: This study demonstrates that an autologous MSC-seeded PDOvalved transannular patch restores at mid-term a living and functional RVOT, withsynthesis of a viable layered tissue close to that of the native RVOT. Such anapproach may ultimately lead to applications in the treatment of congenital heartdiseases involving the RVOT.125
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AATS FUTURE MEETINGSMay 1-5, 2010Me
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Boston - American Association for Thoracic Surgery

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