PMID- 36358333 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221126 IS - 2079-7737 (Print) IS - 2079-7737 (Electronic) IS - 2079-7737 (Linking) VI - 11 IP - 11 DP - 2022 Nov 8 TI - Molecular Characterization of Secreted Factors and Extracellular Vesicles-Embedded miRNAs from Bone Marrow-Derived Mesenchymal Stromal Cells in Presence of Synovial Fluid from Osteoarthritis Patients. LID - 10.3390/biology11111632 [doi] LID - 1632 AB - Bone marrow-derived mesenchymal stromal cells (BMSCs)-based therapies show a great potential to manage inflammation and tissue degeneration in osteoarthritis (OA) patients. Clinical trials showed the ability to manage pain and activation of immune cells and allowed restoration of damaged cartilage. To date, a molecular fingerprint of BMSC-secreted molecules in OA joint conditions able to support clinical outcomes is missing; the lack of that molecular bridge between BMSC activity and clinical results hampers clinical awareness and translation into practice. In this study, BMSCs were cultured in synovial fluid (SF) obtained from OA patients and, for the first time, a thorough characterization of soluble factors and extracellular vesicles (EVs)-embedded miRNAs was performed in this condition. Molecular data were sifted through the sieve of molecules and pathways characterizing the OA phenotype in immune cells and joint tissues. One-hundred and twenty-five secreted factors and one-hundred and ninety-two miRNAs were identified. The combined action of both types of molecules was shown to, first, foster BMSCs interaction with the most important OA immune cells, such as macrophages and T cells, driving their switch towards an anti-inflammatory phenotype and, second, promote cartilage homeostasis assisting chondrocyte proliferation and attenuating the imbalance between destructive and protective extracellular matrix-related players. Overall, molecular data give an understanding of the clinical results observed in OA patients and can enable a faster translation of BMSC-based products into everyday clinical practice. FAU - Ragni, Enrico AU - Ragni E AUID- ORCID: 0000-0003-0272-7417 AD - Laboratorio di Biotecnologie applicate all'Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, I-20161 Milan, Italy. FAU - Perucca Orfei, Carlotta AU - Perucca Orfei C AUID- ORCID: 0000-0001-6162-8668 AD - Laboratorio di Biotecnologie applicate all'Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, I-20161 Milan, Italy. FAU - Valli, Federico AU - Valli F AD - Chirurgia Articolare Sostitutiva e Chirurgia Ortopedica (CASCO), IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, I-20161 Milan, Italy. FAU - Zagra, Luigi AU - Zagra L AD - Hip Department, IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, I-20161 Milan, Italy. FAU - de Girolamo, Laura AU - de Girolamo L AUID- ORCID: 0000-0002-9979-3092 AD - Laboratorio di Biotecnologie applicate all'Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, I-20161 Milan, Italy. LA - eng GR - RCR-2021-23671217/Ministero della Salute/ GR - Ricerca Corrente/Ministero della Salute/ PT - Journal Article DEP - 20221108 PL - Switzerland TA - Biology (Basel) JT - Biology JID - 101587988 PMC - PMC9687557 OTO - NOTNLM OT - cartilage OT - extracellular vesicles OT - immune cells OT - mesenchymal stromal cells OT - miRNAs OT - osteoarthritis OT - secretome COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. EDAT- 2022/11/12 06:00 MHDA- 2022/11/12 06:01 PMCR- 2022/11/08 CRDT- 2022/11/11 01:04 PHST- 2022/10/03 00:00 [received] PHST- 2022/11/02 00:00 [revised] PHST- 2022/11/04 00:00 [accepted] PHST- 2022/11/11 01:04 [entrez] PHST- 2022/11/12 06:00 [pubmed] PHST- 2022/11/12 06:01 [medline] PHST- 2022/11/08 00:00 [pmc-release] AID - biology11111632 [pii] AID - biology-11-01632 [pii] AID - 10.3390/biology11111632 [doi] PST - epublish SO - Biology (Basel). 2022 Nov 8;11(11):1632. doi: 10.3390/biology11111632.