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

摘要: Pancreatic islet transplantation is a promising approach in treating insulin-dependent diabetes.1-3 Currently, over 900 patients globally have been transplanted with allografts.4 Islet requires isolating islets from mass pancreatic acinar tissue, which involves extensive tissue manipulation and rigorous regulatory approvals to ensure safe high-quality final product for type 1 diabetes (T1D).5-7 Studies whole organ showed that graft failure was attributed systemic infection due the contamination preservation solution.8-10 The issue further exacerbated isolation, multiple steps, including of pancreas portion duodenum and/or spleen attached, trimming decontamination pancreas, perfusion enzyme, digestion, collection, washing purification, culturing, collection islets.11 Although, process manufacturing carried out current good practice (cGMP) facility, risk introducing at any stage procedure still remains.12-14 Aside media used decontamination, all other solutions throughout isolation are prepared within cGMP facility without addition antimicrobial agents prevent potential allergic reaction recipient. T1D more vulnerable infection, especially after required immunosuppressive regimen allograft rejection.15 Thus, it extremely important take measures during transplantation. With advancement as standardized treatment strategy clinical setting, eventually may require biologic license application so effective would be into patients.6,16 Therefore, sterility testing becomes one critical checkpoints. Hence, understand route rate this implement an prevention plan safety potency preparations. A limited number large-scale studies published regarding issues process,15,17-19 little described effect antiseptic on outcome process. In fact, most recent article related topic 10 years ago,18 evaluated use Cefazolin Amphotericin B However, protocol Clinical Transplantation Consortium centers only uses single antibiotic (Cefazolin) dip decontaminate organ.20 We hypothesize using decrease or eliminate product. Herein, we report comprehensive review analysis rates frequency by specific microbial species.