Encapsulation in hollow fibres of xenogeneic cells engineered to secrete IL-4 or IL-13 ameliorates murine collagen-induced arthritis (CIA)

A strategy of gene therapy using IL-4 or IL-13 xenogeneic transfected cells encapsulated into permeable hollow fibres (HF) was used to treat CIA. Hydr ogel-based hallow fibres were obtained from AN-69 copolymer, already known for its biocompatibility and tolerance in rodents. Permeability to IL-4 and lack of cell leakage from the fibres were ascertained in vitro, and ill vi vo. Chinese hamster ovary (CHO) fibroblasts transfected with mouse IL-4 gen e were encapsulated in HF (6.25 x 10(5) cells/HF). IL-4 was detected in vit ro in the culture supernatant of filled fibres for at least 19 days. IL-4 o r IL-13 transfected CHO cells encapsulated in HF were implanted in the peri toneum of mice on days IL-13 after immunization with type II collagen. Cont rol mice were treated with fibre containing CHO cells transfected with beta -galactosidase (beta gal) gene; a positive control group consisted of mice treated by subcutaneous injection of 10(6) cells on days 10 and 25. Mice we re monitored for signs of arthritis by observers unaware of the status of a nimals. Results of these experiments indicate that severity of the articula r disease was significantly reduced in the groups of mice treated with CHO/ IL-4 or CHO/IL-13 cells encapsulated in HF, compared with control groups re ceiving CHO/beta gal cells encapsulated in HF. Histological analysis confir med these data and extended them to a better inhibitory effect of encapsula ted cells compared with free cells on inflammatory and destructive joint di sease. Moreover, such long-term treatment with HF was well tolerated; macro scopic and histological aspects of peritoneal cavity were moderately inflam matory. Thus, our results may have important implications for clinical use of gene transfected cells as therapeutic agents in the treatment of autoimm une diseases.