TY - JOUR AU - Morgan, Kelly AU - Scharp, David AU - Arulmoli, Jayagowri AU - Sunshine, Hannah AU - Hao, Ergeng PY - 2019 DA - 2019/02/26 TI - Advances in Human Islet Processing: Manufacturing Steps to Achieve Predictable Islet Outcomes from Research Pancreases JO - OBM Transplantation SP - 052 VL - 03 IS - 01 AB - Background This presentation of a six-year study processing human islets for research and transplantation includes a review of multi-center transplant studies identifying key variables critical for successful islet processing and defines standardized processing procedures required to provide highly purified, functional Human Islets. Methods Human islet processing methods are defined in detail with pancreas retrieval, shipping, trimming for processing, collagenase distension, controlled digestion by digestion/filtration method, islet purification and islet culture. Islet processing results are summarized from 27 published reports (2003-2017) from 21 international clinical islet transplant centers with 13 single islet centers and 8 from multi-center clinical trials that averaged islet yields of 5,680 IEQ/Gm (Pre-Purification), 4,101 IEQ/Gm (Post-Purification), and 3,599 IEQ/Gm (Post-Culture) with 59.2% purity at time of islet transplant into the liver. Results Their results were compared to this study of 226 Non-DM (Non-Diabetes Mellitus) donor processing islet yields that averaged 6,942.7±201 IEQ/Gm (Pre-Purification), 5,484.5±199 IEQ/Gm (Post-Purification), and 4,351.0±167 IEQ/Gm (Post-Culture) per pancreas with 90.0% purity at time of islet distribution. Islet processing from 29 Type 2 Diabetes donors resulted in reduced islet yields of 5,797±734 IEQ/Gm (Pre-Purification), 4,371±866 IEQ/Gm (Post-Purification), and 3,323±423 IEQ/Gm (Post-Culture) with similar purity but reduced insulin content. Glucose Stimulated Insulin Release testing in T2D islets showed significantly reduced insulin release at 20mM and 20mM+IBMX versus Non-DM islets and showed significantly reduced Total Stimulated Insulin Release of 0.722±0.142 (T2D) versus 1.069±0.067 ng insulin/ng DNA (Non-DM). Conclusions Of the significant process variables, short Switch Times were predominant in greatly increasing islet yields, GSIR results, and insulin content with any time SN - 2577-5820 UR - https://doi.org/10.21926/obm.transplant.1901052 DO - 10.21926/obm.transplant.1901052 ID - Morgan2019 ER -