ABSTRACT
Transplantation of encapsulated porcine islets is proposed to treat type 1 diabetes. However, the envelopment of fibrous tissue and the infiltration of immune cells impair islet function and eventually cause implant failure. It is known that hemodialysis using an ethylene vinyl alcohol (EVOH) membrane results in minor tissue responses. Therefore, we hypothesized that using a low-adhesive EVOH membrane for encapsulation may prevent host cell accumulation and fibrous capsule formation. In this study, rat islets suspended in chitosan gel were encapsulated in bags made from highly porous EVOH membranes, and their in vitro insulin secretion function as well as in vivo performance was evaluated. The results showed that the EVOH bag did not affect islet survival or glucose-stimulated insulin secretion. Whereas naked islets were dysfunctional after 7 days of culture in vitro, islets within the EVOH bag produced insulin continuously for 30 days. Streptozotocin-induced diabetic mice were given islets-chitosan gel-EVOH implants intraperitoneally (650-800 islets equivalent) and exhibited lower blood glucose levels and regained body weight during a 4-week observation period. The transplanted mice had higher levels of serum insulin and C-peptide, with an improved blood glucose disappearance rate. Retrieved implants had minor tissue adhesion, and histology showed a limited number of mononuclear cells and fibroblasts surrounding the implants. No invasion of host cells into the EVOH bags was noticed, and the encapsulated islets were intact and positive for insulin-glucagon immunostaining. In conclusion, an EVOH bag can protect encapsulated islets, limit fibrous capsule formation, and extend graft function.
Subject(s)
Cells, Immobilized/metabolism , Diabetes Mellitus, Experimental/therapy , Diabetes Mellitus, Type 1/therapy , Insulin/metabolism , Islets of Langerhans Transplantation/methods , Islets of Langerhans/metabolism , Animals , Blood Glucose , Body Weight , Cell Survival , Graft Survival , Mice , Polyvinyls , Rats , Treatment OutcomeABSTRACT
Recently, the use of filters has come into light for sanitizing water plants. This study investigated the role of heat-tolerant ultrafilters (UFs) for the remediation of reverse osmosis (RO) plants using periodic thermal disinfection. Two completely identical RO plants (RO plants A and B) were installed in 2006 for surgical hand antisepsis in the operating theater. RO water was stored in the 300 L storage tank and recirculated in the 190 meter-long loop delivering water to 12 faucets in each RO plant. Periodic thermal disinfection came into practice periodically when a UF module was retrofitted to the recirculation loop of each RO plant in 2010. Endotoxin was monitored closely before and after thermal disinfection. Before UF modules were retrofitted, endotoxin increased to a maximum of 0.301 EU/mL in RO plant A and 1.446 EU/mL in RO plant B after thermal disinfection, respectively. Since a UF module was retrofitted to each RO plant in 2010, endotoxin has been continuously below 0.025 EU/mL in RO plant A and exceeded this level five times in RO plant B. On one occasion, endotoxin increased in all samples collected simultaneously after solenoid valves were replaced in the recirculation loop near the air conditioner outlet. At this time, the inside of the pipework was exposed to the ventilation airflow. After the valves were replaced again, this time with the workplace isolated using a curing sheet, endotoxin decreased. On the other occasions, endotoxin increased only in one sample and decreased after thermal disinfection. Annually replaced UF modules were examined twice for estimating the amounts of immobilized endotoxin. The estimated amounts decreased in 2013 by the order of 10-3 in comparison with those in 2011 in both RO plants. The present study suggested that UFs acted synergistically with periodic thermal disinfection for the remediation of RO plants.
