Immunomodulatory potential of secretome from cartilage cells and mesenchymal stromal cells in an arthritic context: From predictive fiction toward reality

Alessandra Colombini; Francesca Libonati; Silvia Lopa; Enrico Ragni; Paola De Luca; Luigi Zagra; Federico Sinigaglia; Matteo Moretti; Laura de Girolamo

doi:10.3389/fmed.2022.992386

Immunomodulatory potential of secretome from cartilage cells and mesenchymal stromal cells in an arthritic context: From predictive fiction toward reality

Front Med (Lausanne). 2022 Oct 12:9:992386. doi: 10.3389/fmed.2022.992386. eCollection 2022.

Authors

Affiliations

¹ Laboratorio di Biotecnologie Applicate all'Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.
² Cell and Tissue Engineering Laboratory, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.
³ Hip Department, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.
⁴ Regenerative Medicine Technologies Lab, Laboratories for Translational Research (LRT), Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
⁵ Department of Surgery, Service of Orthopaedics and Traumatology, Ente Ospedaliero Cantonale, Lugano, Switzerland.
⁶ Faculty of Biomedical Sciences, Euler Institute, USI, Lugano, Switzerland.

Abstract

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.

Keywords: adipose stem cells; bone marrow stem cells; cartilage cells; early osteoarthritis; immunomodulation; miRNAs; secretome.