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. Hydrogel-based hollow 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 in vivo. Chinese hamster ovary (CHO) fibroblasts transfected with mouse IL-4 gene were encapsulated in HF (6.25 x 105 cells/HF). IL-4 was detected in vitro in the culture supernatant of filled fibres for at least 19 days. IL-4 or IL-13 transfected CHO cells encapsulated in HF were implanted in the peritoneum of mice on days 11-13 after immunization with type II collagen. Control mice were treated with fibre containing CHO cells transfected with beta-galactosidase (betagal) gene; a positive control group consisted of mice treated by subcutaneous injection of 106 cells on days 10 and 25. Mice were monitored for signs of arthritis by observers unaware of the status of animals. Results of these experiments indicate that severity of the articular 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 receiving CHO/betagal cells encapsulated in HF. Histological analysis confirmed these data and extended them to a better inhibitory effect of encapsulated cells compared with free cells on inflammatory and destructive joint disease. Moreover, such long-term treatment with HF was well tolerated; macroscopic and histological aspects of peritoneal cavity were moderately inflammatory. Thus, our results may have important implications for clinical use of gene transfected cells as therapeutic agents in the treatment of autoimmune diseases.
Bessis
N
N
Groupe de Recherche en Immunopathologie et Immuno-intervention, UFR Léonard de Vinci, Université Paris-Nord, Bobigny, France.
Honiger
J
J
Damotte
D
D
Minty
A
A
Fournier
C
C
Fradelizi
D
D
Boissier
M
M
D000180:Acrylic Resins; D000181:Acrylonitrile / Q000031:analogs & derivatives*; D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D016466:CHO Cells / Q000637:transplantation*; D006224:Cricetinae; D015316:Genetic Therapy / Q000295:instrumentation / Q000379:methods*; D006367:HeLa Cells / Q000637:transplantation; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics* / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008567:Membranes, Artificial; D051379:Mice; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010539:Permeability; D014162:Transfection; D014183:Transplantation, Heterologous / Q000295:instrumentation / Q000379:methods*
D000180:Acrylic Resins; D018793:Interleukin-13; D008567:Membranes, Artificial; D015847:Interleukin-4; C016892:AN-69; D000181:Acrylonitrile