Drs. Maumus and Gabusi contributed equally to this work.
Adipose-Derived Mesenchymal Stem Cells Exert Antiinflammatory Effects on Chondrocytes and Synoviocytes From Osteoarthritis Patients Through Prostaglandin E2
Article first published online: 23 APR 2013
Copyright © 2013 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 65, Issue 5, pages 1271–1281, May 2013
How to Cite
Manferdini, C., Maumus, M., Gabusi, E., Piacentini, A., Filardo, G., Peyrafitte, J.-A., Jorgensen, C., Bourin, P., Fleury-Cappellesso, S., Facchini, A., Noël, D. and Lisignoli, G. (2013), Adipose-Derived Mesenchymal Stem Cells Exert Antiinflammatory Effects on Chondrocytes and Synoviocytes From Osteoarthritis Patients Through Prostaglandin E2. Arthritis & Rheumatism, 65: 1271–1281. doi: 10.1002/art.37908
- Issue published online: 23 APR 2013
- Article first published online: 23 APR 2013
- Accepted manuscript online: 22 FEB 2013 10:42AM EST
- Manuscript Accepted: 12 FEB 2013
- Manuscript Received: 17 SEP 2012
- European Seventh Framework Programme (project ADIPOA;). Grant Numbers: Health-2009-1.4-3, 241719
To examine the effect of different sources of Good Manufacturing Practice clinical grade adipose-derived mesenchymal stem cells (AD-MSCs) on inflammatory factors in osteoarthritic (OA) chondrocytes and synoviocytes.
AD-MSCs from infrapatellar Hoffa fat, subcutaneous (SC) hip fat, and SC abdominal fat were cocultured in Transwells with chondrocytes or synoviocytes. Inflammatory factors (interleukin-1β [IL-1β], tumor necrosis factor α, IL-6, CXCL1/growth-related oncogene α, CXCL8/IL-8, CCL2/monocyte chemotactic protein 1, CCL3/macrophage inflammatory protein 1α, and CCL5/RANTES) were evaluated by quantitative reverse transcription–polymerase chain reaction or multiplex bead–based immunoassay. The role of different immunomodulators was analyzed.
All the inflammatory factors analyzed were down-modulated at the messenger RNA or protein level independently by all 3 AD-MSC sources or by allogeneic AD-MSCs used in coculture with chondrocytes or synoviocytes. Inflammatory factor down-modulation was observed only when AD-MSCs were cocultured with chondrocytes or synoviocytes that produced high levels of inflammatory factors, but no effect was observed in cells that produced low levels of those factors, thus highlighting a dependence of the AD-MSC effect on existing inflammation. The immunomodulators IL-10, IL-1 receptor antagonist, fibroblast growth factor 2, indoleamine 2,3-dioxygenase 1, and galectin 1 were not involved in AD-MSC effects, whereas the cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathway exerted a role in the mechanism of antiinflammatory AD-MSC action.
The antiinflammatory effects of AD-MSCs are probably not dependent on AD-MSC adipose tissue sources and donors but rather on the inflammatory status of OA chondrocytes and synoviocytes. AD-MSCs seem to be able to sense and respond to the local environment. Even though a combination of different molecules may be involved in AD-MSC effects, the COX-2/PGE2 pathway may play a role, suggesting that AD-MSCs may be useful for therapies in osteoarticular diseases.