Synovial activation is evident in a substantial subpopulation of patients with early osteoarthritis (OA) and has been associated with pathophysiology and clinical symptoms of OA. Previous studies have shown that synovial activation is involved in mediating cartilage destruction during experimental OA. Recently it has been shown that Adipose-derived Stroma/Stem Cells (ASCs) express immunosuppressive characteristics. The aim of our study was to explore the effect of intra-articular injection of ASCs on synovial activation and cartilage destruction during experimental OA.
ASCs were isolated from inguinal fat surrounding the popliteal lymph nodes and cultured for two weeks according to standard procedures. Experimental OA was induced by injection of collagenase into murine knee joints, which causes instability and cartilage destruction. Collagenase-induced OA is characterized by thickening and activation of the synovial lining layer. ASCs were injected into knee joints at various time-points after induction of OA. OA phenotypes were measured within 8 weeks after induction. Total knee joints were isolated and processed for histology. Synovial activation was measured using an arbitrary scale (0 to 3) and cartilage destruction was measured in 4 different layers of the knee joint (medial and lateral tibia and femur) according to the scoring method of Pritzker et al.. Damage to the cruciate ligaments was scored using an arbitrary scale (0 to 5). Moreover, cartilage formation was assessed by quantification of proteoglycans in Safranin O stained sections, using an arbitrary scale (0 to 5).
A single dose of ASCs (20x103 in mouse serum) was injected into the knee joint of mice, 7 days after induction of osteoarthritis. Histology showed that synovial activation was significantly inhibited at day 14 (9%) and day 42 (35%) when compared to serum treated joints. Destruction of cartilage was also significantly inhibited at day 14 (54%) and at day 42 (35%). Inhibition of cartilage destruction was particularly found in the medial tibia. Interestingly, ASC-treatment had a protective effect on the cruciate ligaments. At day 42, damage to the ligaments was reduced by nearly 50% in the ASC treated joints when compared to controls. In line with that, 88% of the serum injected animals showed a dislocation of the knee joint, in contrast to only 25% of the ASC treated animals. Strikingly, new formation of cartilage was 50% lower in the ASC treated animals. In contrast to early treatment, injection of the same dose of ASCs, 14 days after induction of OA only showed a small inhibiting effect (11%) on synovial activation when measured at day 42. Although cartilage destruction diminished with 28%, these values did not reach significance at that time-point.
Our study indicates that a single injection of ASCs into the knee joints of mice with collagenase-induced osteoarthritis gives protection of synovial activation and cartilage destruction when given shortly (day 7) after induction of experimental OA, probably by protecting cruciate ligament destruction.
Disclosure: M. C. ter Huurne, None; P. L. E. M. van Lent, None; A. B. Blom, None; R. Blattes, None; Y. Jeanson, None; L. Casteilla, None; C. Jorgensen, None; W. B. van den Berg, None.