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 language | English |
|---|---|
| Article number | 101463 |
| Journal | Stem Cell Research |
| Volume | 38 |
| DOIs | |
| Publication status | Published - Jul 1 2019 |
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Keywords
- Adipose-derived stromal cells
- Chondrocytes
- Hypertrophy
- MMPs
- Secretome
- TIMPs
ASJC Scopus subject areas
- Developmental Biology
- Cell Biology
Cite this
Adipose-derived stromal cell secretome reduces TNFα-induced hypertrophy and catabolic markers in primary human articular chondrocytes. / Niada, Stefania; Giannasi, Chiara; Gomarasca, Marta; Stanco, Deborah; Casati, Sara; Brini, Anna Teresa.
In: Stem Cell Research, Vol. 38, 101463, 01.07.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Adipose-derived stromal cell secretome reduces TNFα-induced hypertrophy and catabolic markers in primary human articular chondrocytes
AU - Niada, Stefania
AU - Giannasi, Chiara
AU - Gomarasca, Marta
AU - Stanco, Deborah
AU - Casati, Sara
AU - Brini, Anna Teresa
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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.
AB - 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.
KW - Adipose-derived stromal cells
KW - Chondrocytes
KW - Hypertrophy
KW - MMPs
KW - Secretome
KW - TIMPs
UR - http://www.scopus.com/inward/record.url?scp=85065740387&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065740387&partnerID=8YFLogxK
U2 - 10.1016/j.scr.2019.101463
DO - 10.1016/j.scr.2019.101463
M3 - Article
C2 - 31108390
AN - SCOPUS:85065740387
VL - 38
JO - Stem Cell Research
JF - Stem Cell Research
SN - 1873-5061
M1 - 101463
ER -