Antiinflammatory and chondroprotective effects of intraarticular injection of adipose-derived stem cells in experimental osteoarthritis

• Published in: Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2012-11, Vol.64 (11), p.3604-3613
• Main Authors: ter Huurne, Menno, Schelbergen, Rik, Blattes, Roxane, Blom, Arjen, de Munter, Wouter, Grevers, Lilyanne C., Jeanson, Jannik, Noël, Danièle, Casteilla, Louis, Jorgensen, Christian, van den Berg, Wim, van Lent, Peter L. E. M.
• Format: Article
• Language: English
• Subjects: Adipose Tissue - cytology; Animals; Anterior Cruciate Ligament - immunology; Anterior Cruciate Ligament - pathology; Arthritis; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cartilage; Cartilage, Articular - immunology; Cartilage, Articular - pathology; Cell Movement - immunology; Chondrocytes - immunology; Chondrocytes - pathology; Chondrogenesis - immunology; Collagenases - pharmacology; Collateral Ligaments - immunology; Collateral Ligaments - pathology; Disease Models, Animal; Diseases of the osteoarticular system; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Injections, Intra-Articular; Knee Joint - immunology; Knee Joint - pathology; Medical sciences; Mice; Mice, Inbred C57BL; Miscellaneous. Osteoarticular involvement in other diseases; Osteoarthritis; Osteoarthritis, Knee - chemically induced; Osteoarthritis, Knee - immunology; Osteoarthritis, Knee - therapy; Pharmacology. Drug treatments; Posterior Cruciate Ligament - pathology; Stem Cell Transplantation - methods; Synovial Membrane - immunology; Synovial Membrane - pathology
• ISSN: 0004-3591; 2326-5191; 1529-0131; 2326-5205
• DOI: 10.1002/art.34626

Objective In experimental collagenase‐induced osteoarthritis (OA) in the mouse, synovial lining macrophages are crucial in mediating joint destruction. It was recently shown that adipose‐derived stem cells (ASCs) express immunosuppressive characteristics. This study was undertaken to explore the effect of intraarticular injection of ASCs on synovial lining thickness and its relation to joint pathology in experimental mouse OA. Methods ASCs were isolated from fat surrounding the inguinal lymph nodes and cultured for 2 weeks. Experimental OA was induced by injection of collagenase into the knee joints of C57BL/6 mice. OA phenotypes were measured within 8 weeks after induction. Histologic analysis was performed, and synovial thickening, enthesophyte formation, and cartilage destruction were measured in the knee joint. Results ASCs were injected into the knee joints of mice 7 days after the induction of collagenase‐induced OA. On day 1, green fluorescent protein–labeled ASCs were attached to the lining layer in close contact with macrophages. Thickening of the synovial lining, formation of enthesophytes associated with medial collateral ligaments, and formation of enthesophytes associated with cruciate ligaments were significantly inhibited on day 42 after ASC treatment, by 31%, 89%, and 44%, respectively. Destruction of cartilage was inhibited on day 14 (65%) and day 42 (35%). In contrast to early treatment, injection of ASCs on day 14 after OA induction showed no significant effect on synovial activation or joint pathology on day 42. Conclusion These findings indicate that a single injection of ASCs into the knee joints of mice with early‐stage collagenase‐induced OA inhibits synovial thickening, formation of enthesophytes associated with ligaments, and cartilage destruction.