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Decellularized allogeneic heart valves demonstrate self-regeneration potential after a long-term preclinical evaluation.
Iop, Laura; Bonetti, Antonella; Naso, Filippo; Rizzo, Stefania; Cagnin, Stefano; Bianco, Roberto; Dal Lin, Carlo; Martini, Paolo; Poser, Helen; Franci, Paolo; Lanfranchi, Gerolamo; Busetto, Roberto; Spina, Michel; Basso, Cristina; Marchini, Maurizio; Gandaglia, Alessandro; Ortolani, Fulvia; Gerosa, Gino.
Afiliação
  • Iop L; Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
  • Bonetti A; Department of Experimental and Clinical Medicine, University of Udine, Udine, Italy.
  • Naso F; Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
  • Rizzo S; Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
  • Cagnin S; Department of Biology and C.R.I.B.I. Biotechnology Centre, University of Padua, Padua, Italy.
  • Bianco R; Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
  • Dal Lin C; Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
  • Martini P; Department of Biology and C.R.I.B.I. Biotechnology Centre, University of Padua, Padua, Italy.
  • Poser H; Department of Animal Medicine, Productions and Health, University of Padua, Legnaro, Italy.
  • Franci P; Department of Animal Medicine, Productions and Health, University of Padua, Legnaro, Italy.
  • Lanfranchi G; Department of Biology and C.R.I.B.I. Biotechnology Centre, University of Padua, Padua, Italy.
  • Busetto R; Department of Animal Medicine, Productions and Health, University of Padua, Legnaro, Italy.
  • Spina M; Department of Biomedical Sciences, University of Padua, Padua, Italy.
  • Basso C; Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
  • Marchini M; Department of Experimental and Clinical Medicine, University of Udine, Udine, Italy.
  • Gandaglia A; Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
  • Ortolani F; Department of Experimental and Clinical Medicine, University of Udine, Udine, Italy.
  • Gerosa G; Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
PLoS One ; 9(6): e99593, 2014.
Article em En | MEDLINE | ID: mdl-24940754
ABSTRACT
Tissue-engineered heart valves are proposed as novel viable replacements granting longer durability and growth potential. However, they require extensive in vitro cell-conditioning in bioreactor before implantation. Here, the propensity of non-preconditioned decellularized heart valves to spontaneous in body self-regeneration was investigated in a large animal model. Decellularized porcine aortic valves were evaluated for right ventricular outflow tract (RVOT) reconstruction in Vietnamese Pigs (n = 11) with 6 (n = 5) and 15 (n = 6) follow-up months. Repositioned native valves (n = 2 for each time) were considered as control. Tissue and cell components from explanted valves were investigated by histology, immunohistochemistry, electron microscopy, and gene expression. Most substitutes constantly demonstrated in vivo adequate hemodynamic performances and ex vivo progressive repopulation during the 15 implantation months without signs of calcifications, fibrosis and/or thrombosis, as revealed by histological, immunohistochemical, ultrastructural, metabolic and transcriptomic profiles. Colonizing cells displayed native-like phenotypes and actively synthesized novel extracellular matrix elements, as collagen and elastin fibers. New mature blood vessels, i.e. capillaries and vasa vasorum, were identified in repopulated valves especially in the medial and adventitial tunicae of regenerated arterial walls. Such findings correlated to the up-regulated vascular gene transcription. Neoinnervation hallmarks were appreciated at histological and ultrastructural levels. Macrophage populations with reparative M2 phenotype were highly represented in repopulated valves. Indeed, no aspects of adverse/immune reaction were revealed in immunohistochemical and transcriptomic patterns. Among differentiated elements, several cells were identified expressing typical stem cell markers of embryonic, hematopoietic, neural and mesenchymal lineages in significantly higher number and specific topographic distribution in respect to control valves. Following the longest follow-up ever realized in preclinical models, non-preconditioned decellularized allogeneic valves offer suitable microenvironment for in vivo cell homing and tissue remodeling. Manufactured with simple, timesaving and cost-effective procedures, these promising valve replacements hold promise to become an effective alternative, especially for pediatric patients.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regeneração / Próteses Valvulares Cardíacas / Implante de Prótese de Valva Cardíaca Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regeneração / Próteses Valvulares Cardíacas / Implante de Prótese de Valva Cardíaca Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article