Background Thickening of the synovial lining layer comprising macrophages expressing an activated phenotype is evident in a substantial subpopulation of patients with early OA and has been associated with pathophysiology and clinical symptoms of osteoarthritis. Previous studies have shown that synovial macrophages are crucial in mediating cartilage destruction and osteophyte formation in murine collagenase-induced osteoarthritis (CiOA). 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.
Objectives To explore the effect of intra-articular injection of ADSCs on synovial thickness, cartilage destruction and osteophyte formation during murine CiOA.
Methods Adipose derived stem cells (ADSCs) were isolated from fat surrounding the popliteal lymph nodes and cultured according to standard procedures. ADSC were cultured for twee weeks and characterized by FACS analysis CiOA was induced by injection of collagenase into murine knee joints, which causes instability and cartilage destruction and is characterized by synovial lining thickening. ADSCs were injected into knee joints at various time-points after induction of CiOA. 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 osteophyte formation in cruciate and medial collateral ligaments using image analysis.
Results A single dose of ADSCs (20×103 in 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. 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 osteophyte formation assiocated with ligaments. At day 42, the formation of osteophytes in medial collateral and cruciate ligaments was inhibited by 92% and 43% respectively. In contrast to early treatment, injection of the same dose of ADSCs at days 14 after induction of OA, only had a small inhibiting effect (11%) on synovial activation when measured at day 42. Although cartilage destruction diminished with 28% and osteophyte formation with 23%, these values did not reach significancy suggesting that at day 14 damage is already so severe that it cannot be reversed by ADSCs treatment.
Conclusions 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 osteophyte formation when given at day 7 but not at day 14 after onset probably by inhibiting the activated phenotype of synovial macrophages.
Disclosure of Interest None Declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.