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Boston - American Association for Thoracic Surgery

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89 TH ANNUAL MEETING MAY 9–MAY 13, 2009BOSTON, MASSACHUSETTST5. Tissue Engineered Vascular Grafts in Humans: CorrelatingClinical Outcomes to Vascular Neotissue Formation in MiceNarutoshi Hibino, 1 Edward McGillicuddy, 1 Tai Yi, 1 Goki Matsumura, 2Uji Naito, 2 Hiromi Kurosawa, 2* Christopher Breuer, 1 Toshiharu Shinoka 1*1. Yale University School of Medicine, New Haven, CT, USA; 2. Tokyo Women’sMedical University, Tokyo, JapanInvited Discussant: John E. Mayer, Jr.OBJECTIVE: The development of a tissue engineered vascular graft (TEVG) thatpossesses the ability to grow holds great promise <strong>for</strong> advancing the field of cardiacsurgery. In 2001, we initiated a human trial evaluating the use of TEVGs as conduitsin patients with single ventricle physiology. Concurrently, we developed andoptimized a murine model to investigate the mechanisms underlying vascular neotissue<strong>for</strong>mation. This study correlates the clinical feasibility and long term outcomesof TEVGs in humans with the basic biology of vascular neotissue <strong>for</strong>mationin mice.METHODS: Human Trial: Autologous bone marrow (BM) mononuclear cellswere seeded onto a biodegradable tubular scaffold fabricated from a polyglycolicacid (PGA) mesh coated with a co-polymer of l-lactide and -caprolactone (P(LA/CL)).Twenty-five TEVGs were implanted as extracardiac total cavopulmonary connections(EC TCPCs) in patients with single ventricle abnormalities. Patient age rangedfrom 1 to 24 years (median: 5.5 years). Post-operatively, patients were followed byserial angiography and/or CT. Mouse Model: Biodegradable PGA-P(LA/CL) scaffolds,0.6 mm in diameter, were implanted into the IVC in mice (N = 12). Six scaffoldswere seeded with murine BM prior to implantation and six scaffolds wereimplanted unseeded. Following implantation, grafts were followed with serialultrasonography. All mice were sacrificed 14 days following implantation <strong>for</strong> histologicalanalysis of the grafts.RESULTS: Human Trial: There was no graft-related mortality during the followupperiod (mean 4.2 years). There was no evidence of aneurysm <strong>for</strong>mation, graftrupture, or ectopic calcification. Five patients (20%) developed silent graft stenoseswhich did not require intervention. Two conduits (8%) developed critical graftstenoses that were successfully treated with balloon angioplasty. Mouse Model:All seeded grafts remained patent, while 5 unseeded grafts (83%) developed significantstenoses. Seeded grafts expressed von Willebrand factor on the luminalaspect, consistent with early endotheliazation. Unseeded grafts, however, demonstrateddense populations of cells expressing smooth muscle actin, trans<strong>for</strong>minggrowth factor-beta, and macrophage-3 antigen consistent with macrophage-driveninflammation.CONCLUSION: In humans undergoing EC TCPC, use of TEVGs is associatedwith acceptable morbidity and mortality. In mice, BM seeded grafts demonstrateincreased patency, early endotheliazation, and an attenuated inflammatoryresponse compared to unseeded grafts.* AATS Member204

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