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

被引:2
作者
Russo, Valentina [1 ]
Prencipe, Giuseppe [1 ]
Mauro, Annunziata [1 ]
El Khatib, Mohammad [1 ]
Haidar-Montes, Arlette A. [1 ]
Cambise, Nico [1 ,2 ]
Turriani, Maura [1 ]
Stoeckl, Johannes [3 ]
Steinberger, Peter [3 ]
Lancia, Loreto [4 ]
Schnabelrauch, Matthias [5 ]
Berardinelli, Paolo [1 ]
Barboni, Barbara [1 ]
机构
[1] Univ Teramo, Fac Biosci & Agrofood & Environm Technol, Unit Basic & Appl Sci, Via Renato Balzarini 1, I-64100 Teramo, Italy
[2] Assut Europe SpA, Res & Dev Dept, I-67062 Laquila, Italy
[3] Med Univ Vienna, Inst Immunol, Ctr Pathophysiol Infectiol & Immunol, A-1090 Vienna, Austria
[4] Univ Aquila, Dept Biotechnol & Appl Clin Sci, I-67100 Laquila, Italy
[5] Dept Biomat, INNOVENT eV, D-07745 Jena, Germany
基金
欧盟地平线“2020”;
关键词
Tenogenic differentiation; Paracrine effect; 3D electrospun PLGA scaffolds; Amniotic epithelial stem cells (AECs); Immunomodulation; TGF-BETA; REPAIR; TRANSPLANTATION; PROLIFERATION; TENDINOPATHY; RECRUITMENT; TENOMODULIN; MECHANISMS; PROMOTES; MUSCLE;
D O I
10.1016/j.mtbio.2024.101001
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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 (CM(3D)vs. CTR, p < 0.001) and LPS-mediated Jurkat activation with respect to controls (CM3D and CM(2D)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.
引用
收藏
页数:14
相关论文
共 66 条
[1]   Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4) [J].
Achen, MG ;
Jeltsch, M ;
Kukk, E ;
Mäkinen, T ;
Vitali, A ;
Wilks, AF ;
Alitalo, K ;
Stacker, SA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (02) :548-553
[2]   Loss of Tenomodulin Results in Reduced Self-Renewal and Augmented Senescence of Tendon Stem/Progenitor Cells [J].
Alberton, Paolo ;
Dex, Sarah ;
Popov, Cvetan ;
Shukunami, Chisa ;
Schieker, Matthias ;
Docheva, Denitsa .
STEM CELLS AND DEVELOPMENT, 2015, 24 (05) :597-609
[3]  
[Anonymous], 2009, J Biomech Sci Eng, V4, P481, DOI DOI 10.1299/JBSE.4.481
[4]   Placental Stem Cells from Domestic Animals: Translational Potential and Clinical Relevance [J].
Barboni, B. ;
Russo, V. ;
Berardinelli, P. ;
Mauro, A. ;
Valbonetti, L. ;
Sanyal, H. ;
Canciello, A. ;
Greco, L. ;
Muttini, A. ;
Gatta, V. ;
Stuppia, L. ;
Mattioli, M. .
CELL TRANSPLANTATION, 2018, 27 (01) :93-116
[5]   Achilles Tendon Regeneration Can Be Improved by Amniotic Epithelial Cell Allotransplantation [J].
Barboni, B. ;
Russo, V. ;
Curini, V. ;
Mauro, A. ;
Martelli, A. ;
Muttini, A. ;
Bernabo, N. ;
Valbonetti, L. ;
Marchisio, M. ;
Di Giacinto, O. ;
Berardinelli, P. ;
Mattioli, M. .
CELL TRANSPLANTATION, 2012, 21 (11) :2377-2395
[6]   Therapeutic potential of hAECs for early Achilles tendon defect repair through regeneration [J].
Barboni, Barbara ;
Russo, Valentina ;
Gatta, Valentina ;
Bernabo, Nicola ;
Berardinelli, Paolo ;
Mauro, Annunziata ;
Martelli, Alessandra ;
Valbonetti, Luca ;
Muttini, Aurelio ;
Di Giacinto, Oriana ;
Turriani, Maura ;
Silini, Antonietta ;
Calabrese, Giuseppe ;
Abate, Michele ;
Parolini, Ornella ;
Stuppia, Liborio ;
Mattioli, Mauro .
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, 2018, 12 (03) :E1594-E1608
[7]   Indirect Co-Culture with Tendons or Tenocytes Can Program Amniotic Epithelial Cells towards Stepwise Tenogenic Differentiation [J].
Barboni, Barbara ;
Curini, Valentina ;
Russo, Valentina ;
Mauro, Annunziata ;
Di Giacinto, Oriana ;
Marchisio, Marco ;
Alfonsi, Melissa ;
Mattioli, Mauro .
PLOS ONE, 2012, 7 (02)
[8]   Exosomes Derived From Kartogenin-Preconditioned Mesenchymal Stem Cells Promote Cartilage Formation and Collagen Maturation for Enthesis Regeneration in a Rat Model of Chronic Rotator Cuff Tear [J].
Cai, Jiangyu ;
Xu, Junjie ;
Ye, Zipeng ;
Wang, Liren ;
Zheng, Ting ;
Zhang, Tianlun ;
Li, Yufeng ;
Jiang, Jia ;
Zhao, Jinzhong .
AMERICAN JOURNAL OF SPORTS MEDICINE, 2023, 51 (05) :1267-1276
[9]   Molecular mechanisms of T cell co-stimulation and co-inhibition [J].
Chen, Lieping ;
Flies, Dallas B. .
NATURE REVIEWS IMMUNOLOGY, 2013, 13 (04) :227-242
[10]   Amnion-Derived Teno-Inductive Secretomes: A Novel Approach to Foster Tendon Differentiation and Regeneration in an Ovine Model [J].
Citeroni, Maria Rita ;
Mauro, Annunziata ;
Ciardulli, Maria Camilla ;
Di Mattia, Miriam ;
El Khatib, Mohammad ;
Russo, Valentina ;
Turriani, Maura ;
Santer, Michael ;
Della Porta, Giovanna ;
Maffulli, Nicola ;
Forsyth, Nicholas R. ;
Barboni, Barbara .
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, 2021, 9