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| Repair of The Right Ventricular Outflow Tract By a Mesenchymal Stem Cell-Seeded Bioabsorbable Valved Patch: Medium-Term Follow-Up In A Growing Lamb Model | |
David Kalfa1, Alain Bel2, Annabel Chen-Tournoux1, Philippe Rochereau1, Cyrielle Coz1, Valérie Bellamy1, Elie Mousseaux3, Patrick Bruneval4, Jérôme Larghero5, Philippe Menasché1; 1INSERM U633, Paris, France; 2Hôpital Européen Georges Pompidou, Department of Cardiovascular Surgery; University Paris Descartes, Paris, France; 3Hôpital Européen Georges Pompidou, Department of Radiology; University Paris Descartes, Paris, France; 4Hôpital Européen Georges Pompidou, Department of Pathology; University Paris Descartes, Paris, France; 5Hôpital Saint-Louis, Laboratory of Cell Therapy; University Paris Diderot, Paris, France
Methods: Autologous peripheral blood-derived MSCs were phenotypically characterized, labeled with quantum dots, seeded onto monocusp-fitted PDO bioabsorbable patches and cultured for 6 days. These patches were implanted in a transannular position into the RVOT of 6 growing lambs (group I), with 1, 4, or 8 months of follow-up. Unseeded PDO valved patches (group II, n=2) and autologous pericardial patches fitted with a polytetrafluoroethylene monocusp (group III, n=2) were used as controls. Morphological and functional data on the RVOT were evaluated by echocardiography (US) and MRI. Explanted specimens were assessed by gross examination, histology, immunohistochemistry and calcium content 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% (16mm→18,9mm) in group I. Gross examination and biochemical assays of cell-seeded patches demonstrated a better tissue growing, less retraction, less fibrosis and less calcifications 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 PDO scaffold, a viable, layered, endothelialized tissue (Figure) and an extracellular matrix (with elastic fibers) comparable to that native ovine tissue. The neo-tissue that reconstituted the RVOT exhibited environment-dependent differentiation patterns: the proximal portion of the patch harbored cells expressing cardiac myosin whereas its distal segment harbored α-smooth muscle actin (SMA)-expressing myofibroblasts. Only group I patches demonstrated cells with an endothelial phenotype (vW factor) on the luminal surface. Quantum dots were found in vWF- or α-SMA-positive cells at 1 month, thereby suggesting that at least some of them were donor-derived. Conclusion: This study demonstrates that an autologous MSC-seeded PDO valved transannular patch restores at mid-term a living and functional RVOT, with synthesis of a viable layered tissue close to that of the native RVOT. Such an approach may ultimately lead to applications in the treatment of congenital heart diseases involving the RVOT.  Hematoxylin-Eosin staining of the vascular (pulmonary artery) 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 is completely degraded, and a viable layered tissue similar to 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, degenerated and surrounded by a dense inflammatory tissue. Magnification : x5. Back to 2009 Annual Meeting Back to Program Outline Back to Main Program |
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