Session Title: Rheumatoid Arthritis: Animal Models
Session Type: Abstract Submissions (ACR)
Background/Purpose: Even though treatment of rheumatoid arthritis (RA) has emerged, aiming bone repair is still a challenge. Mesenchymal stem cells (MSCs) possess immunoregulatory function with pluripotency and efficacy on arthritis animal models has been reported by intra-venous or intra-peritoneal administration. Herein we have utilized nano-fiber poly-lactic-co-glycollic acid (PLGA) scaffold known for controlled biodegradability with less immunogenicity as an effective delivery system of MSCs to the arthritic joint.
Methods: MSCs were simply injected intra-articularly (IA) or intra-peritoneally (IP) or seeded on nano-fiber PLGA scaffold and implanted into bilateral ankles (IMP) of collagen-induced arthritis (CIA) rats at the time of immunization. Efficacy was evaluated clinically (arthritis score, body weight and hind paw thickness), radiologically (X-ray and micro-CT) and histologically (Hematoxilin-Eosin staining).
Results: Treatment of CIA with IMP significantly decreased the severity of arthritis while IA and IP showed less or no effect. Radiologic evaluation of bone destruction was also suppressed by IMP, but not by IA or IP. Histological analysis of the ankles indicated less inflammatory cell infiltration, synovial hyperplasia, pannus formation, resulting in less destruction of the cartilage and bone by IMP compared to IA and IP. Interestingly, size and weight of the spleen, draining lymph nodes in rats treated with IMP were significantly smaller than those treated with IA and IP. These phenomena were observed at both early phase (2 weeks after immunization) and late phase (6 weeks after immunization) of the disease course. Histological analysis of the draining lymph nodes revealed less or no chronic inflammation in the early phase and reduced germinal center formation at the late phase in rats treated with IMP compared to IA and IP treatment.
Conclusion: Local delivery of MSCs with nano-fiber PLGA scaffold significantly suppress arthritis and bone destruction with decreased immune response in the draining lymph node, while IA or IP had less or no effect. The amount of MSCs that we utilized in our study was far lower compared to the studies reported previously. Therefore, our results suggest the importance of MSCs to reside at the local inflammatory site for suppressing the inflammation and moreover regenerating the destructed bone sequentially.
Mitsubishi-Tanabe Pharma Corporation, Abbott Japan Co., Ltd., Eisai Co., Ltd., Chugai Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Santen Pharmaceutical Co., Ltd., Pfizer Japan Inc., Astellas Pharma Inc., Daiichi-Sankyo Co., Ltd., GlaxoSmithKlin,
Bristol-Myers Squibb, MSD K.K., Chugai Pharmaceutical Co., Ltd., Mitsubishi-Tanabe Pharma Corporation, Astellas Pharma Inc., Abbott Japan Co., Ltd., Eisai Co., Ltd. and Janssen Pharmaceutical K.K,
Otsuka Pharmaceutical Co., Ltd,,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/delivering-mesenchymal-stem-cells-to-arthritic-joints-with-nano-fiber-scaffold-resulted-in-inhibition-of-arthritis-and-joint-damage-in-arthritis-models/