Adipose-derived stromal cell secretome reduces TNFα-induced hypertrophy and catabolic markers in primary human articular chondrocytes

Stefania Niada, Chiara Giannasi, Marta Gomarasca, Deborah Stanco, Sara Casati, Anna Teresa Brini

Research output: Contribution to journalArticlepeer-review

Abstract

Recent clinical trials show the efficacy of Adipose-derived Stromal Cells (ASCs) in contrasting the osteoarthritis scenario. Since it is quite accepted that ASCs act predominantly through a paracrine mechanism, their secretome may represent a valid therapeutic substitute. The aim of this study was to investigate the effects of ASC conditioned medium (ASC-CM) on TNFα-stimulated human primary articular chondrocytes (CHs). CHs were treated with 10 ng/ml TNFα and/or ASC-CM (1:5 recipient:donor cell ratio). ASC-CM treatment blunted TNFα-induced hypertrophy, reducing the levels of Osteocalcin (−37%), Collagen X (−18%) and MMP-13 activity (−61%). In addition, it decreased MMP-3 activity by 59%. We showed that the reduction of MMP activity correlates to the abundance of TIMPs (Tissue Inhibitors of MMPs) in ASC secretome (with TIMP-1 exceeding 200 ng/ml and TIMP-2/3 in the ng/ml range) rather than to a direct down-modulation of the expression and/or release of these proteases. In addition, ASC secretome contains high levels of other cartilage protecting factors, i.e. OPG and DKK-1. ASC-CM comprises cartilage-protecting factors and exerts anti-hypertrophic and anti-catabolic effects on TNFα-stimulated CHs in vitro. Our results support a future use of this cell-derived but cell-free product as a therapeutic approach in the management of osteoarthritis.

Original languageEnglish
Article number101463
JournalStem Cell Research
Volume38
DOIs
Publication statusPublished - Jul 1 2019

Keywords

  • Adipose-derived stromal cells
  • Chondrocytes
  • Hypertrophy
  • MMPs
  • Secretome
  • TIMPs

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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