Immunomodulatory potential of secretome from cartilage cells and mesenchymal stromal cells in an arthritic context: From predictive fiction toward reality
The purpose of the present study is to predict by bioinformatics the activity of the extracellular vesicle (EV)-embedded micro RNA (miRNAs) secreted by cartilage cells (CCs), adipose tissue-derived- (ASCs), and bone marrow-derived stem cells (BMSCs) and verify their immunomodulatory potential suppor...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.992386/full |
| _version_ | 1798020781372866560 |
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| author | Alessandra Colombini Francesca Libonati Silvia Lopa Enrico Ragni Paola De Luca Luigi Zagra Federico Sinigaglia Matteo Moretti Matteo Moretti Matteo Moretti Matteo Moretti Laura de Girolamo |
| author_facet | Alessandra Colombini Francesca Libonati Silvia Lopa Enrico Ragni Paola De Luca Luigi Zagra Federico Sinigaglia Matteo Moretti Matteo Moretti Matteo Moretti Matteo Moretti Laura de Girolamo |
| author_sort | Alessandra Colombini |
| collection | DOAJ |
| description | The purpose of the present study is to predict by bioinformatics the activity of the extracellular vesicle (EV)-embedded micro RNA (miRNAs) secreted by cartilage cells (CCs), adipose tissue-derived- (ASCs), and bone marrow-derived stem cells (BMSCs) and verify their immunomodulatory potential supporting our bioinformatics findings to optimize the autologous cell-based therapeutic strategies for osteoarthritis (OA) management. Cells were isolated from surgical waste tissues of three patients who underwent total hip replacement, expanded and the EVs were collected. The expression of EV-embedded miRNA was evaluated with the QuantStudio 12 K Flex OpenArray® platform. Mientournet and ingenuity pathway analysis (IPA) were used for validated target prediction analysis and to identify miRNAs involved in OA and inflammation. Cells shared the expression of 325 miRNAs embedded in EVs and differed for the expression of a small number of them. Mienturnet revealed no results for miRNAs selectively expressed by ASCs, whereas miRNA expressed by CCs and BMSCs were putatively involved in the modulation of cell cycle, senescence, apoptosis, Wingless and Int-1 (Wnt), transforming growth factor beta (TGFβ), vascular endothelial growth factor (VEGF), Notch, Hippo, tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL-1β), insulin like growth factor 1 (IGF-1), RUNX family transcription factor 2 (RUNX2), and endochondral ossification pathways. Cartilage homeostasis, macrophages and T cells activity and inflammatory mediators were identified by IPA as targets of the miRNAs found in all the cell populations. Co-culture tests on macrophages and T cells confirmed the immuno-modulatory ability of CCs, ASCs, and BMSCs. The study findings support the rationale behind the use of cell-based therapy for the treatment of OA. |
| first_indexed | 2024-04-11T17:03:18Z |
| format | Article |
| id | doaj.art-0edafc9b952e440ba4348cdbd7456fec |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-11T17:03:18Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-0edafc9b952e440ba4348cdbd7456fec2022-12-22T04:13:07ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-10-01910.3389/fmed.2022.992386992386Immunomodulatory potential of secretome from cartilage cells and mesenchymal stromal cells in an arthritic context: From predictive fiction toward realityAlessandra Colombini0Francesca Libonati1Silvia Lopa2Enrico Ragni3Paola De Luca4Luigi Zagra5Federico Sinigaglia6Matteo Moretti7Matteo Moretti8Matteo Moretti9Matteo Moretti10Laura de Girolamo11Laboratorio di Biotecnologie Applicate all’Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Milan, ItalyLaboratorio di Biotecnologie Applicate all’Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Milan, ItalyCell and Tissue Engineering Laboratory, IRCCS Istituto Ortopedico Galeazzi, Milan, ItalyLaboratorio di Biotecnologie Applicate all’Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Milan, ItalyLaboratorio di Biotecnologie Applicate all’Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Milan, ItalyHip Department, IRCCS Istituto Ortopedico Galeazzi, Milan, ItalyLaboratorio di Biotecnologie Applicate all’Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Milan, ItalyCell and Tissue Engineering Laboratory, IRCCS Istituto Ortopedico Galeazzi, Milan, ItalyRegenerative Medicine Technologies Lab, Laboratories for Translational Research (LRT), Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandDepartment of Surgery, Service of Orthopaedics and Traumatology, Ente Ospedaliero Cantonale, Lugano, SwitzerlandFaculty of Biomedical Sciences, Euler Institute, USI, Lugano, SwitzerlandLaboratorio di Biotecnologie Applicate all’Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Milan, ItalyThe purpose of the present study is to predict by bioinformatics the activity of the extracellular vesicle (EV)-embedded micro RNA (miRNAs) secreted by cartilage cells (CCs), adipose tissue-derived- (ASCs), and bone marrow-derived stem cells (BMSCs) and verify their immunomodulatory potential supporting our bioinformatics findings to optimize the autologous cell-based therapeutic strategies for osteoarthritis (OA) management. Cells were isolated from surgical waste tissues of three patients who underwent total hip replacement, expanded and the EVs were collected. The expression of EV-embedded miRNA was evaluated with the QuantStudio 12 K Flex OpenArray® platform. Mientournet and ingenuity pathway analysis (IPA) were used for validated target prediction analysis and to identify miRNAs involved in OA and inflammation. Cells shared the expression of 325 miRNAs embedded in EVs and differed for the expression of a small number of them. Mienturnet revealed no results for miRNAs selectively expressed by ASCs, whereas miRNA expressed by CCs and BMSCs were putatively involved in the modulation of cell cycle, senescence, apoptosis, Wingless and Int-1 (Wnt), transforming growth factor beta (TGFβ), vascular endothelial growth factor (VEGF), Notch, Hippo, tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL-1β), insulin like growth factor 1 (IGF-1), RUNX family transcription factor 2 (RUNX2), and endochondral ossification pathways. Cartilage homeostasis, macrophages and T cells activity and inflammatory mediators were identified by IPA as targets of the miRNAs found in all the cell populations. Co-culture tests on macrophages and T cells confirmed the immuno-modulatory ability of CCs, ASCs, and BMSCs. The study findings support the rationale behind the use of cell-based therapy for the treatment of OA.https://www.frontiersin.org/articles/10.3389/fmed.2022.992386/fulladipose stem cellsbone marrow stem cellssecretomemiRNAsearly osteoarthritisimmunomodulation |
| spellingShingle | Alessandra Colombini Francesca Libonati Silvia Lopa Enrico Ragni Paola De Luca Luigi Zagra Federico Sinigaglia Matteo Moretti Matteo Moretti Matteo Moretti Matteo Moretti Laura de Girolamo Immunomodulatory potential of secretome from cartilage cells and mesenchymal stromal cells in an arthritic context: From predictive fiction toward reality Frontiers in Medicine adipose stem cells bone marrow stem cells secretome miRNAs early osteoarthritis immunomodulation |
| title | Immunomodulatory potential of secretome from cartilage cells and mesenchymal stromal cells in an arthritic context: From predictive fiction toward reality |
| title_full | Immunomodulatory potential of secretome from cartilage cells and mesenchymal stromal cells in an arthritic context: From predictive fiction toward reality |
| title_fullStr | Immunomodulatory potential of secretome from cartilage cells and mesenchymal stromal cells in an arthritic context: From predictive fiction toward reality |
| title_full_unstemmed | Immunomodulatory potential of secretome from cartilage cells and mesenchymal stromal cells in an arthritic context: From predictive fiction toward reality |
| title_short | Immunomodulatory potential of secretome from cartilage cells and mesenchymal stromal cells in an arthritic context: From predictive fiction toward reality |
| title_sort | immunomodulatory potential of secretome from cartilage cells and mesenchymal stromal cells in an arthritic context from predictive fiction toward reality |
| topic | adipose stem cells bone marrow stem cells secretome miRNAs early osteoarthritis immunomodulation |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.992386/full |
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