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.
Adipose-derived stromal cell secretome reduces TNFα-induced hypertrophy and catabolic markers in primary human articular chondrocytes / S. Niada, C. Giannasi, M. Gomarasca, D. Stanco, S. Casati, A.T. Brini. - In: STEM CELL RESEARCH. - ISSN 1873-5061. - (2019). [Epub ahead of print]
Titolo: | Adipose-derived stromal cell secretome reduces TNFα-induced hypertrophy and catabolic markers in primary human articular chondrocytes |
Autori: | GIANNASI, CHIARA (Co-primo) CASATI, SARA (Penultimo) BRINI, ANNA TERESA (Ultimo) |
Parole Chiave: | Adipose-derived stromal cells; Secretome; Chondrocytes; Hypertrophy; MMPs; TIMPs |
Settore Scientifico Disciplinare: | Settore BIO/14 - Farmacologia Settore BIO/13 - Biologia Applicata |
Data di pubblicazione: | 2019 |
Rivista: | |
Tipologia: | Article (author) |
Data ahead of print / Data di stampa: | 15-mag-2019 |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.scr.2019.101463 |
Appare nelle tipologie: | 01 - Articolo su periodico |
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