Comparison of two ASC-derived therapeutics in an in vitro OA model: secretome versus extracellular vesicles: Stem Cell Research and Therapy

C. Giannasi, S. Niada, C. Magagnotti, E. Ragni, A. Andolfo, A.T. Brini

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In the last years, several clinical trials have proved the safety and efficacy of adipose-derived stem/stromal cells (ASC) in contrasting osteoarthritis (OA). Since ASC act mainly through paracrine mechanisms, their secretome (conditioned medium, CM) represents a promising therapeutic alternative. ASC-CM is a complex cocktail of proteins, nucleic acids, and lipids released as soluble factors and/or conveyed into extracellular vesicles (EV). Here, we investigate its therapeutic potential in an in vitro model of OA. Methods: Human articular chondrocytes (CH) were induced towards an OA phenotype by 10 ng/ml TNFα in the presence of either ASC-CM or EV, both deriving from 5 × 105 cells, to evaluate the effect on hypertrophic, catabolic, and inflammatory markers. Results: Given the same number of donor cells, our data reveal a higher therapeutic potential of ASC-CM compared to EV alone that was confirmed by its enrichment in chondroprotective factors among which TIMP-1 and -2 stand out. In details, only ASC-CM significantly decreased MMP activity (22% and 29% after 3 and 6 days) and PGE2 expression (up to 40% at day 6) boosted by the inflammatory cytokine. Conversely, both treatments down-modulated of ~ 30% the hypertrophic marker COL10A1. Conclusions: These biological and molecular evidences of ASC-CM beneficial action on CH with an induced OA phenotype may lay the basis for its future clinical translation as a cell-free therapeutic in the management of OA. © 2020, The Author(s).
Original languageEnglish
Article number521
JournalStem Cell Res. Ther.
Volume11
Issue number1
DOIs
Publication statusPublished - 2020

Keywords

  • Adipose-derived stem/stromal cells
  • Chondrocytes
  • Extracellular vesicles
  • Hypertrophy
  • MMP
  • Osteoarthritis
  • PGE2
  • Secretome

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