Session Title: Biology and Pathology of Bone and Joint: Osteoarthritis
Session Type: Abstract Submissions (ACR)
OA lesions are treated with mesenchymal stem cells aiming to enhance tissue repair by transformation to eg. chondrocytes. Recently it has been shown that adipose derived stem cells (ADSC) express strong immunosuppressive characteristics which might impair the activated phenotype of synovial OA macrophages. Previous studies have shown that synovial macrophages are crucial in mediating cartilage destruction and enthesophyte formation in murine collagenase-induced osteoarthritis (CiOA). In the present study we explored the effect of intra-articular injection of ADSCs on synovium, cartilage destruction and enthesophyte formation during murine CiOA.
Adipose derived stem cells (ADSCs) were isolated from fat surrounding the popliteal lymph nodes and were injected into knee joints at day 7 after induction of CiOA. CiOA was induced by injection of collagenase into murine knee joints, which causes instability and joint destruction and is characterized by synovial lining thickening. Mediators present in washouts of synovium were measured using Luminex. OA phenotypes were measured within 8 weeks after induction. Total knee joints were isolated and performed for histology. Synovial activation was measured using an arbitrary scale of 0-3, cartilage destruction according to the scorings method of Pritzker et al (2006) and enthesophyte formation in cruciate and medial collateral ligaments using image analysis.
A single dose of ADSCs (20X103in mouse serum) was injected into the knee joint of mice, 7 days after induction of collagenase-induced osteoarthritis. Histology showed that thickness of the synovial lining layer, which is characteristic for this model, was significantly inhibited by ADSCs treatment at day 14 (9%) and day 42 (35%) when compared to control (serum) treated OA joints. This was in line with significant lower levels of IL-1β (53%) and S100A8/A9 (51%) (no effect on TNFα and IL-6) in synovial washouts measured at day 14 after treatment. Destruction of cartilage was significantly lower both at day 14 (55%) and day 42 (35%) and was particularly found in the medial tibia. Strikingly, ADSCs treatment had a protective effect on enthesophyte formation assiocated with ligaments. At day 42, the formation of enthesophytes in medial collateral and cruciate ligaments was inhibited by 92% and 43% respectively. Intra-articular injection of GFP-labeled ADSCs into day 7 OA knee joints, showed that stem cells were clearly detected within the synovial intima in close interaction with macrophages.
Our study indicates that a single injection of ADSCs into the knee joints of mice with CiOA gives protection of synovial activation, cartilage destruction and enthesophyte formation when given at day 7 after onset probably by inhibiting the activated phenotype of synovial macrophages.
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/intra-articular-injection-of-adipose-derived-stem-cells-inhibits-activation-of-the-synovium-and-protects-against-cartilage-damage-and-enthesophyte-formation-in-murine-experimental-osteoarthritis/