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Nanopatterned acellular valve conduits drive the commitment of blood-derived multipotent cells

Authors Di Liddo R, Aguiari P, Barbon S, Bertalot T, Mandoli A, Tasso A, Schrenk S, Iop L, Gandaglia A, Parnigotto PP, Conconi MT, Gerosa G

Received 28 June 2016

Accepted for publication 30 July 2016

Published 12 October 2016 Volume 2016:11 Pages 5041—5055

DOI https://doi.org/10.2147/IJN.S115999

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Yu Mi

Peer reviewer comments 3

Editor who approved publication: Dr Thomas J Webster


Rosa Di Liddo,1,2 Paola Aguiari,3 Silvia Barbon,1,2 Thomas Bertalot,1 Amit Mandoli,1 Alessia Tasso,1 Sandra Schrenk,1 Laura Iop,3 Alessandro Gandaglia,3 Pier Paolo Parnigotto,2 Maria Teresa Conconi,1,2 Gino Gerosa3

1Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 2Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling ONLUS, 3Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy


Abstract: Considerable progress has been made in recent years toward elucidating the correlation among nanoscale topography, mechanical properties, and biological behavior of cardiac valve substitutes. Porcine TriCol scaffolds are promising valve tissue engineering matrices with demonstrated self-repopulation potentiality. In order to define an in vitro model for investigating the influence of extracellular matrix signaling on the growth pattern of colonizing blood-derived cells, we cultured circulating multipotent cells (CMC) on acellular aortic (AVL) and pulmonary (PVL) valve conduits prepared with TriCol method and under no-flow condition. Isolated by our group from Vietnamese pigs before heart valve prosthetic implantation, porcine CMC revealed high proliferative abilities, three-lineage differentiative potential, and distinct hematopoietic/endothelial and mesenchymal properties. Their interaction with valve extracellular matrix nanostructures boosted differential messenger RNA expression pattern and morphologic features on AVL compared to PVL, while promoting on both matrices the commitment to valvular and endothelial cell-like phenotypes. Based on their origin from peripheral blood, porcine CMC are hypothesized in vivo to exert a pivotal role to homeostatically replenish valve cells and contribute to hetero- or allograft colonization. Furthermore, due to their high responsivity to extracellular matrix nanostructure signaling, porcine CMC could be useful for a preliminary evaluation of heart valve prosthetic functionality.

Keywords: blood-derived multipotent cells, self-repopulation potential, guided tissue engineering, TriCol decellularization procedure, ECM nanostructure signaling

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