515 Use of Encapsulated Cells Secreting Murine TIMP-2 Ameliorates Collagen-Induced Arthritis in Mice NICOLE RENGGLI-ZULLIGER, a JEAN DUDLER, a NOBORU FUJIMOTO, b KAZUSHI IWATA, b AND ALEXANDER SO a,c a Department of Rheumatology, CHUV, 1011 Lausanne, Switzerland b Biopharmaceutical Department, Fuji Chemical Industries, Ltd., Takaoka, Toyama 933-8511, Japan INTRODUCTION Arthritis is characterized by an irreversible process of connective tissue break- down in the joints, leading to permanent loss of function and disability. If most ther- apies are efficient at relieving pain and inflammation, we still are unable to control the underlying process of destruction. It is believed that an altered equilibrium be- tween matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the joints leads to the pathologic destruction of cartilage and bone. 1 Based on this assumption, several studies in various pathologies have investigated the therapeutic potential of restoring the balance between enzymes and inhibitors by increasing the amount of circulating inhibitors. 2,3 In this work, prevention of cartilage breakdown was evaluated in vivo in a murine collagen-induced arthritis model (CIA). Inhibition of MMPs was realized by the subcutaneous implantation of two 1-cm-long semipermeable hollow fibers (cap- sules) containing cells overexpressing murine TIMP-2 (mTIMP-2). MATERIAL AND METHODS Induction of Collagen-Induced Arthritis (CIA) Male DBA/1J (H-2q) mice between 8–10 weeks of age were obtained from BRL/ RCC Biotechnology & Animal Breeding (Füllinsdorf, Switzerland). 100 μg of native chicken type II collagen (M.M. Griffith; Utah, USA) emulsified in Complete Fre- und’s Adjuvant (Difco; Basel, Switzerland) was injected intradermally at base of tail. At day 24 after the first injection, a booster injection of 100 μg of native chicken type II collagen was done in Incomplete Freund’s Adjuvant. Clinical scoring was done blindly as described elsewhere. 4 c Corresponding author: Professor Alexander So, Department of Rheumatology, Centre Hospi- talier Universitaire Vaudois, CH-1011 Lausanne, Switzerland. Phone, +41 21 314 14 49; fax, +41 21 314 15 33; e-mail, aso@chuv.hospvd.ch