title: The influence of heart valve leaflet matrix characteristics on the interaction between human mesenchymal stem cells and decellularized scaffolds.
abstract: The potential for in vitro colonization of decellularized valves by human bone marrow mesenchymal stem cells (hBM-MSCs) towards the anisotropic layers ventricularis and fibrosa and in homo- vs. heterotypic cell-ECM interactions has never been investigated. hBM-MSCs were expanded and characterized by immunofluorescence and FACS analysis. Porcine and human pulmonary valve leaflets (p- and hPVLs, respectively) underwent decellularization with Triton X100-sodium cholate treatment (TRICOL), followed by nuclear fragment removal. hBM-MSCs (2x10(6) cells/cm(2)) were seeded onto fibrosa (FS) or ventricularis (VS) of decellularized PVLs, precoated with FBS and fibronectin, and statically cultured for 30 days. Bioengineered PVLs revealed no histopathological features but a reconstructed endothelium lining and the presence of fibroblasts, myofibroblasts and SMCs, as in the corresponding native leaflet. The two valve layers behaved differently as regards hBM-MSC repopulation potential, however, with a higher degree of 3D spreading and differentiation in VS than in FS samples, and with enhanced cell survival and colonization effects in the homotypic ventricularis matrix, suggesting that hBM-MSC phenotypic conversion is strongly influenced in vitro by the anisotropic valve microstructure and species-specific matching between extracellular matrix and donor cells. These findings are of particular relevance to in vivo future applications of valve tissue engineering.
authors.affiliation: Department of Cardiologic, Thoracic and Vascular Sciences, School of Medicine, University of Padua, Via Giustiniani, 2 - I-35128 Padua, Italy. laura.iop@unipd.it
authors.forename: Laura
authors.initials: L
authors.lastname: Iop
authors.forename: Vera
authors.initials: V
authors.lastname: Renier
authors.forename: Filippo
authors.initials: F
authors.lastname: Naso
authors.forename: Martina
authors.initials: M
authors.lastname: Piccoli
authors.forename: Antonella
authors.initials: A
authors.lastname: Bonetti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gandaglia
authors.forename: Michela
authors.initials: M
authors.lastname: Pozzobon
authors.forename: Adolfo
authors.initials: A
authors.lastname: Paolin
authors.forename: Fulvia
authors.initials: F
authors.lastname: Ortolani
authors.forename: Maurizio
authors.initials: M
authors.lastname: Marchini
authors.forename: Michele
authors.initials: M
authors.lastname: Spina
authors.forename: Paolo
authors.initials: P
authors.lastname: De Coppi
authors.forename: Saverio
authors.initials: S
authors.lastname: Sartore
authors.forename: Gino
authors.initials: G
authors.lastname: Gerosa
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D040761:Biomimetic Materials; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000737:chemistry*; D006350:Heart Valve Prosthesis; D006351:Heart Valves / Q000737:chemistry / Q000648:ultrastructure*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D010641:Phenotype; D011474:Prosthesis Design; D013552:Swine; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*; D054457:Tissue Scaffolds; D055815:Young Adult
chemical_list: D015415:Biomarkers