Secreted Factors and Extracellular Vesicles Account for the Immunomodulatory and Tissue Regenerative Properties of Bone-Marrow-Derived Mesenchymal Stromal Cells for Osteoarthritis

Cells. 2022 Nov 4;11(21):3501. doi: 10.3390/cells11213501.

Abstract

Bone-marrow-derived mesenchymal stromal cells (BMSCs) showed therapeutic potential in the treatment of musculoskeletal diseases, including osteoarthritis (OA). Their soluble mediators and extracellular vesicles (EVs), which make up the secretome, suppress immune response, attenuate inflammation and promote cartilage repair. EVs, as well as the whole secretome, have been investigated as cell free approaches for OA although, to date, a disease-tailored molecular fingerprint is missing. In this study, soluble mediators and miRNAs were sifted in the BMSCs' secretome and EVs, respectively, and analyzed in the frame of cell types and factors involved in OA. The majority of identified molecules repress the activation of immune cells and the production of OA-related inflammatory mediators, as well as promote cartilage protection by acting on both chondrocytes homeostasis and extracellular matrix-degrading enzymes. These data provide the molecular ground for the therapeutic potential of BMSCs for regenerative applications for OA and support the use of secretome or EVs as cell-free applications in joint diseases.

Keywords: bone marrow; extracellular vesicles; mesenchymal stromal cells; miRNA; osteoarthritis; secretome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow
  • Extracellular Vesicles* / metabolism
  • Humans
  • Immunity
  • Mesenchymal Stem Cells* / metabolism
  • Osteoarthritis* / metabolism
  • Osteoarthritis* / therapy

Grants and funding

The work reported in this publication was funded by the Italian Ministry of Health, RCR-2021-23671217 project under the Italian Musculoskeletal Apparatus Network RAMS and Ricerca Corrente. The APC was funded by the Italian Ministry of Health, RCR-2021-23671217 project under the Italian Musculoskeletal Apparatus Network RAMS and Ricerca Corrente.