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

作者: Stefania Niada , Chiara Giannasi , Marta Gomarasca , Deborah Stanco , Sara Casati

DOI: 10.1016/J.SCR.2019.101463

关键词:

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

参考文章(45)
Zhi-yun Feng, Zhen-nian He, Bin Zhang, Yi-qiao Li, Jian Guo, Yuan-lin Xu, Ming-yuan Han, Zhong Chen, Adenovirus-mediated osteoprotegerin ameliorates cartilage destruction by inhibiting proteoglycan loss and chondrocyte apoptosis in rats with collagen-induced arthritis. Cell and Tissue Research. ,vol. 362, pp. 187- 199 ,(2015) , 10.1007/S00441-015-2194-8
Tatsuyoshi M. Kono, Emily K. Sims, Dan R. Moss, Wataru Yamamoto, Geonyoung Ahn, Julie Diamond, Xin Tong, Kathleen H. Day, Paul R. Territo, Helmut Hanenberg, Dmitry O. Traktuev, Keith L. March, Carmella Evans-Molina, Human Adipose‐Derived Stromal/Stem Cells Protect Against STZ‐Induced Hyperglycemia: Analysis of hASC‐Derived Paracrine Effectors Stem Cells. ,vol. 32, pp. 1831- 1842 ,(2014) , 10.1002/STEM.1676
Denise L. Cecil, C. Thomas G. Appleton, Monika D. Polewski, John S. Mort, Ann Marie Schmidt, Alison Bendele, Frank Beier, Robert Terkeltaub, The Pattern Recognition Receptor CD36 Is a Chondrocyte Hypertrophy Marker Associated with Suppression of Catabolic Responses and Promotion of Repair Responses to Inflammatory Stimuli Journal of Immunology. ,vol. 182, pp. 5024- 5031 ,(2009) , 10.4049/JIMMUNOL.0803603
Cl Manferdini, M Maumus, E Gabusi, F Paolella, F Grassi, C Jorgensen, S Fleury-Cappellesso, Danièle Noël, G Lisignoli, Lack of anti-inflammatory and anti-catabolic effects on basal inflamed osteoarthritic chondrocytes or synoviocytes by adipose stem cell-conditioned medium. Osteoarthritis and Cartilage. ,vol. 23, pp. 2045- 2057 ,(2015) , 10.1016/J.JOCA.2015.03.025
Hwanhee Oh, Churl-Hong Chun, Jang-Soo Chun, Dkk-1 expression in chondrocytes inhibits experimental osteoarthritic cartilage destruction in mice Arthritis & Rheumatism. ,vol. 64, pp. 2568- 2578 ,(2012) , 10.1002/ART.34481
Cristina Manferdini, Marie Maumus, Elena Gabusi, Anna Piacentini, Giuseppe Filardo, Julie-Anne Peyrafitte, Christian Jorgensen, Philippe Bourin, Sandrine Fleury-Cappellesso, Andrea Facchini, Danièle Noël, Gina Lisignoli, Adipose-derived mesenchymal stem cells exert antiinflammatory effects on chondrocytes and synoviocytes from osteoarthritis patients through prostaglandin E2. Arthritis & Rheumatism. ,vol. 65, pp. 1271- 1281 ,(2013) , 10.1002/ART.37908
Kevin B.L. Lee, James H.P. Hui, Im Chim Song, Lenny Ardany, Eng Hin Lee, Injectable mesenchymal stem cell therapy for large cartilage defects--a porcine model. Stem Cells. ,vol. 25, pp. 2964- 2971 ,(2007) , 10.1634/STEMCELLS.2006-0311
Ralf Lichtinghagen, Petra B Musholt, Michael Lein, Andreas Römer, Birgit Rudolph, Glen Kristiansen, Steffen Hauptmann, Dietmar Schnorr, Stefan A Loening, Klaus Jung, Different mRNA and Protein Expression of Matrix Metalloproteinases 2 and 9 and Tissue Inhibitor of Metalloproteinases 1 in Benign and Malignant Prostate Tissue European Urology. ,vol. 42, pp. 398- 406 ,(2002) , 10.1016/S0302-2838(02)00324-X
Marie Maumus, Cristina Manferdini, Karine Toupet, Julie-Anne Peyrafitte, Rosanna Ferreira, Andrea Facchini, Elena Gabusi, Philippe Bourin, Christian Jorgensen, Gina Lisignoli, Danièle Noël, Adipose mesenchymal stem cells protect chondrocytes from degeneration associated with osteoarthritis Stem Cell Research. ,vol. 11, pp. 834- 844 ,(2013) , 10.1016/J.SCR.2013.05.008
Yusuke Egashira, Sou Sugitani, Yukiya Suzuki, Keisuke Mishiro, Kazuhiro Tsuruma, Masamitsu Shimazawa, Shinichi Yoshimura, Toru Iwama, Hideaki Hara, The conditioned medium of murine and human adipose-derived stem cells exerts neuroprotective effects against experimental stroke model. Brain Research. ,vol. 1461, pp. 87- 95 ,(2012) , 10.1016/J.BRAINRES.2012.04.033