SCIENCE@home

Advances in Human Islet Processing: Manufacturing Steps to Achieve Predictable Islet Outcomes from Research Pancreases

D. Scharp,Jayagowri Arulmoli,K. Morgan,Hannah Sunshine,E. Hao

Published 2018 in OBM Transplantation

ABSTRACT

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. OBM Transplantation 2019; 3(1), doi:10.21926/obm.transplant.1901052 Page 2/73 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 <10 minutes with Donor Age and Body Mass Index also important. Increased Cold Ischemia times decreased islet yields and insulin content. In terms of pancreas preservation solutions, University of Wisconsin solution (UW) use was most effective for optimal islet quantity, quality, and function post preservation.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-57 of 57 references · Page 1 of 1

CITED BY

Showing 1-11 of 11 citing papers · Page 1 of 1