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

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.

journal_name

Stem Cell Res

journal_title

Stem cell research

authors

Niada S,Giannasi C,Gomarasca M,Stanco D,Casati S,Brini AT

doi

10.1016/j.scr.2019.101463

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

101463

eissn

1873-5061

issn

1876-7753

pii

S1873-5061(19)30093-5

journal_volume

38

pub_type

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