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

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.

Single-nucleus RNA sequencing of human pancreatic islets identifies novel gene sets and distinguishes β-cell subpopulations with dynamic transcriptome profiles

“…Adult human pancreatic islets from seven brain-dead donors were generated by Prodo Laboratories (Aliso Viejo, CA) according to the standard procedures [ 25 ]. Islets were harvested from pancreata from deceased organ donors without any identifying information and with informed consent properly and legally secured, and Western Institutional Review Board (WIRB) approval.…”

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“…The complexity of pancreas transplant viability reminds scientists and clinicists that there are other perspectives and alternatives to PTx -bioengineering and islets auto transplantation, when it is possible [58][59][60].…”

Islet Transplantation: How Much Have We Advanced and How to Keep Moving Forward?

“…Although islet isolation protocols have advanced considerably over the last 30 years, there are several areas of opportunity to improve islet quality and quantity. In this special issue, a comprehensive multicenter and multi-year report by Scharp et al [1] summarizes several factors that have been shown to be consistently associated with improved islet yield, as well as insulin responsiveness and content, including active enzyme digestion time (i.e., switch time), older age and longer ischemia time. This relevant work by Sharp et al challenges the notion that islet isolation techniques have 'reached their peak' and are unlikely to be amenable to substantial improvements.…”