The influence of heart valve leaflet matrix characteristics on the interaction between human mesenchymal stem cells and decellularized scaffolds.
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.
Iop
Laura
L
Department of Cardiologic, Thoracic and Vascular Sciences, School of Medicine, University of Padua, Via Giustiniani, 2 - I-35128 Padua, Italy. laura.iop@unipd.it
Renier
Vera
V
Naso
Filippo
F
Piccoli
Martina
M
Bonetti
Antonella
A
Gandaglia
Alessandro
A
Pozzobon
Michela
M
Paolin
Adolfo
A
Ortolani
Fulvia
F
Marchini
Maurizio
M
Spina
Michele
M
De Coppi
Paolo
P
Sartore
Saverio
S
Gerosa
Gino
G
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
D015415:Biomarkers