Menno ter Huurne1, R. Schelbergen2, Roxane Blattes3, Arjen B. Blom2, W. de Munter2, Lilyanne C. Grevers2, Jannik Jeanson3, Danièle Noël4, Louis Casteilla3, Christian Jørgensen4, W. van den Berg2, Peter L. E. M. van Lent5
1Radboud University Nijmegen Medical Centre, the Netherlands
2Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
3INSERM U1031, STROMALab UPS‐CNRS‐EFS UMR5273 Toulouse France
4Inserm, U844, Hôpital Saint-Eloi Montpellier, France.
5Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, 272, Geert Grooteplein 28, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Tóm tắt
AbstractObjectiveIn 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.MethodsASCs 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.ResultsASCs 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.ConclusionThese 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.
