Department of Surgery
China Medical University Hospital
Factors significantly impacting islet yield from donor pancreata standardized by the North American Donor Score: a retrospective study from the University of Illinois at Chicago islet database
Chun Chieh Yeh1,2, Ling-jia Wang1, James J. McGarrigle1, Yong Wang1, Mustafa Omami1, Arshad Khan1, Diana Gutierrez1, Matt A. Bochenek1, Mohammad Nourmohammadzade1, Joshua Mendoza-Elias1, Benjamin McCracken1, Kevin Hendricks1, Augusta Mikalauskaite1, Gail Skolek1, Gayle Blake1, Mary Polk1, Enza Marchese1, Barbara Barbaro1, Jose Oberholzer1.
1Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, IL, United States; 2School of Medicine and Department of Surgery, China Medical University Hospital, China Medical University, Taichung, Taiwan
Background: Islet transplantation is a procedure in which insulin-producing islets are isolated from the pancreas of a deceased organ donor using both mechanical and enzymatic manipulation. Following the isolation, the islets are then purified, washed, cultured and resuspended prior to transplantation into Type1 DM recipients. An important limitation to this procedure is the variability of the islet yield following the isolation process. Achieving the possibly greatest islet yield per pancreas remains a clinical challenge for islet isolation centers throughout the world. There are two aspects that affect islet yield: donor pancreas quality and islet cell processing techniques. The following is a retrospective study performed to investigate the factors that influence islet isolation outcomes based on donor pancreata standardized using the North American Islet Donor (NAID) score.
Materials and Methods: Originally 630 cases of allogeneic human islet isolation were entered in the University of Illinois at Chicago (UIC) database. To identify relevant manufacturing variables impacting islet yield, and reduce the number of confounders, we then excluded all cases using non-GMP enzymes and CIT cases, as well as the cases with a NAID score < 65. One hundred and nineteen cases remained for further analysis. Multivariate linear regressions were performed to determine factors that influenced pre- and post-purified islet counts and islet quality score. Furthermore, subgroup analysis was performed with multi-variable logistic regression to investigate factors that lead to post-purification- islet equivalent number (IEQ) greater than 400,000 and clinical islet transplantation.
Results: 1) Pre-purified and post-purified islet yield mean values were 605,091 and 570,098 IEQ, respectively for the 40 cases (IEQ ≥400,000) of NAID score >65. Pre-purified and post-purified islet yield mean values were 356,997 and 235,987 IEQ, respectively for the 79 cases (IEQ <400,000) of NAID score >65. 2) NAID score (>80), pancreatic duct cannulation time (<30 min), specific enzyme brand, enzyme perfusion method (mechanical), and collagenase units per gram of pancreatic tissue were all independent factors predicting larger pre-purified islet yield, percentage of pancreatic digestion, and packed tissue volume. 3) Specific enzyme brand and enzyme perfusion via mechanical method were independent factors predicting better pre-purified islet quality score. 4) Cold ischemic time (<10 hours), NAID score (>80), duct cannulation time (<30min) were independent predictors for better post-purified total islet counts. 5) Enzyme brand and duct cannulation times were predictors for post-purified islet quality score. 6) Furthermore, cold ischemic time (<10 vs. ≥10 hours) (Odds Ratio [OR] 3.574, 95% Confidence Interval [CI] 1.529-8.353) and NAID score (>80 vs. 65-80) (OR 2.767, 95% CI 1.145-6.690) were independent determinants for both post-purified islet yield greater than 400,000 IEQ and cases suitable for clinical islet transplantation. See Table 1 for the summary of results.
Conclusion: Analyzing islet isolations using a scoring system for donor pancreata could help to identify the importance of technical issues during the isolation process. Cold ischemic time and NAID score are still of paramount importance for high islet yield and clinical transplantation.
15:30 - 17:00
|Pancreas & Islet Donors: Assessing Risk and Optimizing Outcomes||Factors significantly impacting islet yield from donor pancreata standardized by the North American Donor Score: a retrospective study from the University of Illinois at Chicago islet database||Room 110|