Session Type: Abstract Submissions (ACR)
A substantial subpopulation of patients with early osteoarthritis (OA) show a thickened synovial lining layer comprising macrophages expressing an activated phenotype (reflected by production of IL-1β and S100A8/A9). Recently we have shown that adipose derived stem cells (ADSC) inhibit joint destruction after local application to knee joints with experimental OA . The goal of our study was to explore the effect of synovial activation on the immunosuppressive capacity of ADSCs to modulate joint destruction after local administration to experimental OA knee joints.
ADSCs were isolated from fat surrounding the popliteal lymph nodes and cultured for two weeks. Collagenase induced OA (CIOA) was induced by injection of collagenase into murine knee joints. ADSCs were injected into the same joints at day 7 after induction of OA. Joint destruction was measured within 6 weeks after induction. Total knee joints were isolated and processed for histology. Synovial thickening was measured using an arbitrary scale of 0-3. Synovium was isolated at various time-points after injection of ASC and washouts were measured for S100A8/A9 and IL-1 using Luminex. Chondrogenesis/bone formation inside ligaments was measured using image analysis.
A single dose of ADSCs (20X103) was injected into the knee joint of mice, 7 days after induction of CIOA. Thickening of the synovial lining layer, which is characteristic for this model, was high (2,6+/-1) and was significantly inhibited by ADSC treatment at day 14 (9%) and day 42 (35%) when compared to control (serum) treated OA joints. Washouts of synovium taken at 6 hrs, 48 hrs, day 14 and day 42 after injection of ADSCs showed that protein levels of IL-1ß and S100A8/A9 were significantly decreased already 48 hrs after injection of ADSC (IL-1ß 57% and S100A8/A9 by 22%) and rapidly declined thereafter. Serum levels of S100A8/A9 were inhibited with 85% (from 794+/- 294 to 117+/- 29 ng/ml) at day 14 after ADSC treatment suggesting that the effect on synovial activation is very rapid. Strikingly, ADSCs had a protective effect on chondrogenesis in medial and cruciate ligaments at day 42 after treatment (inhibition 92% and 43% respectively). Next, we explored the effect in a condition with less synovial inflammation. Synovial thickness at day 42 was 62% lower when compared to the former study (from 2.6 +/-1 to 1 +/-0.2) which was reflected by lower S100A8/A9 serum levels (at day 14 around 50 ng/ml compared to 800 ng/ml). Injection of the same dose of ADSCs at day 7 after induction of OA, did not inhibit synovial thickening nor chondrogenesis in the collateral (1.3+/-0.2 versus WT controls 1.1+/-0.3) and cruciate ligaments (1.8+/-0.3 versus WT controls 1.9+/-0.2) when measured at day 42.
Our study indicates that synovial activation rapidly drives anti-inflammatory effects of ADSCs after local administration in murine knee joints with experimental OA and protects against development of ligament damage.
P. L. E. M. van Lent,
M. C. ter Huurne,
A. B. Blom,
W. B. van den Berg,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/synovial-activation-in-experimental-oa-drives-immuno-suppressive-effects-of-adipose-derived-stem-cells-after-local-administration-and-protects-against-chondrogenesis/