Tendon Biomimetic Electrospun PLGA Fleeces Induce an Early Epithelial-Mesenchymal Transition and Tenogenic Differentiation on Amniotic Epithelial Stem Cells

Cells

Marta Di Federico¹  Torsten Walter²  Barbara Barboni²  Jürgen Weisser²  Ralf Wyrwa²  Lisa di Marcantonio³  Matthias Schnabelrauch⁴  Massimo Ancora⁴  Francesco Lazzaro⁵  MariaRita Citeroni⁶  Annunziata Mauro⁶  Mohammad El Khatib⁶  Valentina Russo⁶  Paolo Berardinelli⁶  Cesare Cammà⁶ 

[1] Development Department, Assut Europe S.p.A.,Magliano dei Marsi, 67062 L’Aquila, Italy;Department of Biomaterials, INNOVENT e. V, J-07749 Jena, Germany;Laboratory of Bacteriology, Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise “Giuseppe Caporale”, 64100 Teramo, Italy;Laboratory of Molecular Biology and Genomic, Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise “Giuseppe Caporale, 64100 Teramo, Italy;;Research &Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy;

关键词: aligned fibers;    amniotic epithelial stem cells;    biomimetic scaffold;    electrospinning;    epithelial-mesenchymal transition;    plga;    tendon tissue engineering;    tenogenic differentiation;   

DOI  :  10.3390/cells9020303

来源: DOAJ

【 摘 要 】

Background. The design of tendon biomimetic electrospun fleece with Amniotic Epithelial Stem Cells (AECs) that have shown a high tenogenic attitude may represent an alternative strategy to overcome the unsatisfactory results of conventional treatments in tendon regeneration. Methods. In this study, we evaluated AEC-engineered electrospun poly(lactide-co-glycolide) (PLGA) fleeces with highly aligned fibers (ha-PLGA) that mimic tendon extracellular matrix, their biocompatibility, and differentiation towards the tenogenic lineage. PLGA fleeces with randomly distributed fibers (rd-PLGA) were generated as control. Results. Optimal cell infiltration and biocompatibility with both PLGA fleeces were shown. However, only ha-PLGA fleeces committed AECs towards an Epithelial-Mesenchymal Transition (EMT) after 48 h culture, inducing their cellular elongation along the fibers’ axis and the upregulation of mesenchymal markers. AECs further differentiated towards tenogenic lineage as confirmed by the up-regulation of tendon-related genes and Collagen Type 1 (COL1) protein expression that, after 28 days culture, appeared extracellularly distributed along the direction of ha-PLGA fibers. Moreover, long-term co-cultures of AEC-ha-PLGA bio-hybrids with fetal tendon explants significantly accelerated of half time AEC tenogenic differentiation compared to ha-PLGA fleeces cultured only with AECs. Conclusions. The fabricated tendon biomimetic ha-PLGA fleeces induce AEC tenogenesis through an early EMT, providing a potential tendon substitute for tendon engineering research.

【 授权许可】

Unknown