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, Stefania Niada, Chiara Giannasi, Marta Gomarasca, Deborah Stanco, Sara Casati, Anna Teresa Brini
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.
Keywords: Adipose-derived stromal cells; Chondrocytes; Hypertrophy; MMPs; Secretome; TIMPs.
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
Source: PubMed