Assessing the functional potential of conditioned media derived from amniotic epithelial stem cells engineered on 3D biomimetic scaffolds: An in vitro model for tendon regeneration

Tendon diseases pose a significant challenge in regenerative medicine due to the limited healing capacity of this tissue. Successful tendon regeneration requires a combination of angiogenesis, immune response, and tenogenesis processes. An effective tendon engineering (TE) strategy must finely tune...

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Main Authors: Valentina Russo, Giuseppe Prencipe, Annunziata Mauro, Mohammad El Khatib, Arlette A. Haidar-Montes, Nico Cambise, Maura Turriani, Johannes Stöckl, Peter Steinberger, Loreto Lancia, Matthias Schnabelrauch, Paolo Berardinelli, Barbara Barboni
Format: Article
Language:English
Published: Elsevier 2024-04-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006424000607
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author Valentina Russo
Giuseppe Prencipe
Annunziata Mauro
Mohammad El Khatib
Arlette A. Haidar-Montes
Nico Cambise
Maura Turriani
Johannes Stöckl
Peter Steinberger
Loreto Lancia
Matthias Schnabelrauch
Paolo Berardinelli
Barbara Barboni
author_facet Valentina Russo
Giuseppe Prencipe
Annunziata Mauro
Mohammad El Khatib
Arlette A. Haidar-Montes
Nico Cambise
Maura Turriani
Johannes Stöckl
Peter Steinberger
Loreto Lancia
Matthias Schnabelrauch
Paolo Berardinelli
Barbara Barboni
author_sort Valentina Russo
collection DOAJ
description Tendon diseases pose a significant challenge in regenerative medicine due to the limited healing capacity of this tissue. Successful tendon regeneration requires a combination of angiogenesis, immune response, and tenogenesis processes. An effective tendon engineering (TE) strategy must finely tune this systems’ interplay toward homeostasis.This study explores in vitro the paracrine influence of amniotic epithelial stem cells (AECs) engineered on a validated 3D electrospun PLGA scaffolds on HUVECs (angiogenesis), PBMCs/Jurkat (immune response), and AECs (tenogenic stem cell activation).The results revealed the role of scaffold's topology and topography in significantly modulating the paracrine profile of the cells. In detail, AECs basal release of bioactive molecules was boosted in the cells engineered on 3D scaffolds, in particular VEGF-D, b-FGF, RANTES, and PDGF-BB (p < 0.0001 vs. CMCTR). Moreover, biological tests demonstrated 3D scaffolds' proactive role in potentiating AECs' paracrine inhibition on PBMCs proliferation (CM3D vs. CTR, p < 0.001) and LPS-mediated Jurkat activation with respect to controls (CM3D and CM2D vs. CTR, p < 0.01 and p < 0.05, respectively), without exerting any in vitro pro-angiogenic role in promoting HUVECs proliferation and tubule formation. Teno-inductive paracrine ability of AECs engineered on 3D scaffolds was assessed on co-cultured ones, which formed tendon-like structures. These latter demonstrated an upregulation of tendon-related genes (SCX, THBS4, COL1, and TNMD) and the expression TNMD and COL1 proteins.Overall, this research underscores the pivotal role of the 3D topology and topography of PLGA tendon mimetic scaffolds in orchestrating effective tendon regeneration through modulating cell behavior and crosstalk between engineered stem cells and different subpopulations in the damaged tendon.
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spelling doaj.art-a12a126b76684f3f938188d3c9886f392024-03-18T04:34:24ZengElsevierMaterials Today Bio2590-00642024-04-0125101001Assessing the functional potential of conditioned media derived from amniotic epithelial stem cells engineered on 3D biomimetic scaffolds: An in vitro model for tendon regenerationValentina Russo0Giuseppe Prencipe1Annunziata Mauro2Mohammad El Khatib3Arlette A. Haidar-Montes4Nico Cambise5Maura Turriani6Johannes Stöckl7Peter Steinberger8Loreto Lancia9Matthias Schnabelrauch10Paolo Berardinelli11Barbara Barboni12Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyUnit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyUnit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy; Corresponding author. Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, Via Renato Balzarini 1, 64100, Teramo, Italy.Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyUnit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyUnit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy; Research &amp; Development Department, Assut Europe S.p.A., Magliano dei Marsi, 67062 L'Aquila, ItalyUnit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyCentre for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, 1090 Vienna, AustriaCentre for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, ItalyDepartment of Biomaterials, INNOVENT e. V., 07745 Jena, GermanyUnit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyUnit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyTendon diseases pose a significant challenge in regenerative medicine due to the limited healing capacity of this tissue. Successful tendon regeneration requires a combination of angiogenesis, immune response, and tenogenesis processes. An effective tendon engineering (TE) strategy must finely tune this systems’ interplay toward homeostasis.This study explores in vitro the paracrine influence of amniotic epithelial stem cells (AECs) engineered on a validated 3D electrospun PLGA scaffolds on HUVECs (angiogenesis), PBMCs/Jurkat (immune response), and AECs (tenogenic stem cell activation).The results revealed the role of scaffold's topology and topography in significantly modulating the paracrine profile of the cells. In detail, AECs basal release of bioactive molecules was boosted in the cells engineered on 3D scaffolds, in particular VEGF-D, b-FGF, RANTES, and PDGF-BB (p < 0.0001 vs. CMCTR). Moreover, biological tests demonstrated 3D scaffolds' proactive role in potentiating AECs' paracrine inhibition on PBMCs proliferation (CM3D vs. CTR, p < 0.001) and LPS-mediated Jurkat activation with respect to controls (CM3D and CM2D vs. CTR, p < 0.01 and p < 0.05, respectively), without exerting any in vitro pro-angiogenic role in promoting HUVECs proliferation and tubule formation. Teno-inductive paracrine ability of AECs engineered on 3D scaffolds was assessed on co-cultured ones, which formed tendon-like structures. These latter demonstrated an upregulation of tendon-related genes (SCX, THBS4, COL1, and TNMD) and the expression TNMD and COL1 proteins.Overall, this research underscores the pivotal role of the 3D topology and topography of PLGA tendon mimetic scaffolds in orchestrating effective tendon regeneration through modulating cell behavior and crosstalk between engineered stem cells and different subpopulations in the damaged tendon.http://www.sciencedirect.com/science/article/pii/S2590006424000607Tenogenic differentiationParacrine effect3D electrospun PLGA scaffoldsAmniotic epithelial stem cells (AECs)Immunomodulation
spellingShingle Valentina Russo
Giuseppe Prencipe
Annunziata Mauro
Mohammad El Khatib
Arlette A. Haidar-Montes
Nico Cambise
Maura Turriani
Johannes Stöckl
Peter Steinberger
Loreto Lancia
Matthias Schnabelrauch
Paolo Berardinelli
Barbara Barboni
Assessing the functional potential of conditioned media derived from amniotic epithelial stem cells engineered on 3D biomimetic scaffolds: An in vitro model for tendon regeneration
Materials Today Bio
Tenogenic differentiation
Paracrine effect
3D electrospun PLGA scaffolds
Amniotic epithelial stem cells (AECs)
Immunomodulation
title Assessing the functional potential of conditioned media derived from amniotic epithelial stem cells engineered on 3D biomimetic scaffolds: An in vitro model for tendon regeneration
title_full Assessing the functional potential of conditioned media derived from amniotic epithelial stem cells engineered on 3D biomimetic scaffolds: An in vitro model for tendon regeneration
title_fullStr Assessing the functional potential of conditioned media derived from amniotic epithelial stem cells engineered on 3D biomimetic scaffolds: An in vitro model for tendon regeneration
title_full_unstemmed Assessing the functional potential of conditioned media derived from amniotic epithelial stem cells engineered on 3D biomimetic scaffolds: An in vitro model for tendon regeneration
title_short Assessing the functional potential of conditioned media derived from amniotic epithelial stem cells engineered on 3D biomimetic scaffolds: An in vitro model for tendon regeneration
title_sort assessing the functional potential of conditioned media derived from amniotic epithelial stem cells engineered on 3d biomimetic scaffolds an in vitro model for tendon regeneration
topic Tenogenic differentiation
Paracrine effect
3D electrospun PLGA scaffolds
Amniotic epithelial stem cells (AECs)
Immunomodulation
url http://www.sciencedirect.com/science/article/pii/S2590006424000607
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