Prophylactically Decontaminating Human Islet Product for Safe Clinical Application: Effective and Potent Method

BACKGROUND: Transplanting pancreatic islets into recipients must be safe and effective to treat type 1 diabetes. Islet quality and quantity are important; however, the final product must also be free from microbial contamination and low endotoxin levels. METHODS: This study explored a method to eliminate contamination in manufacturing islets for transplantation. A simple (single antibiotic n = 164) and refined (triple antimicrobial agents, n = 279) pancreas decontaminating methods were used to test their effects on reducing the contamination rates in the islet final product. A total of 443 pancreata were processed for islet isolations. Three samples for microbial tests (Gram stain, aerobic, and anaerobic culture) were taken at preprocess (pancreas preservation), postisolation, and postculture. Endotoxin levels were measured only for islets considered for transplantation. RESULTS: Of 443 pancreata used for islet isolation, 79 (17.8%) showed signs of contamination in preprocess samples; 10 (2.3%) were contaminated in both preprocess and in the final product (postisolation and postculture) samples. Contamination rates in which preprocess and final product samples were positive for contamination was significantly lower using the refined method (refined vs simple method: 5% vs 20.5%, P = 0.045). Identical microbial species were present in both preprocess and in the final product. CONCLUSIONS: This study demonstrated that the refined method reduces the rate of contamination of the islet final product and is safe for clinical application. Moreover, it may be used as a standard method during human islet manufacturing facilitating the application of a biological license agreement from United States Food and Drug Administration.