Human islet isolation optimization: Insights from donor and isolation procedural factors

TL;DR

This study identifies factors affecting islet yield during human islet isolation for transplantation, emphasizing donor characteristics and procedural controls.

Contribution

The study reveals new insights into how donor BMI, height, and procedural temperature control influence islet isolation success.

Findings

Higher donor BMI and height over 170 cm are independently associated with successful islet isolation.

Enzyme perfusion temperature exceeding 14°C for ≥50% of the perfusion duration increases isolation failure risk.

A logistic regression model incorporating body surface area, tissue volume, and digestion time moderately predicts isolation success.

Abstract

This study investigated donor and islet isolation procedural factors influencing the islet yield during human islet isolation for transplantation. We retrospectively analyzed 133 islet isolations from deceased donors performed over 15 years at a single center. Isolations were stratified by post-purification islet yield (≥400,000 islet equivalents [IEQ], successful; <400,000 IEQ, unsuccessful) and by intent (clinical vs research). Higher donor body mass index and height over 170 cm were independently associated with successful isolation, whereas an enzyme perfusion temperature exceeding 14°C for ≥50% of the perfusion duration emerged as an independent risk factor for isolation failure. Clinically intended isolations exhibited tighter thermal control during Phase 1 digestion, greater digestion efficiency, and lower undigested tissue weight. A logistic regression model incorporating body surface area, packed tissue volume, and phase 1 digestion time (the interval from the start of warm recirculation to the collection phase) showed a moderate predictive value for isolation success (area under the curve = 0.755). Subgroup analysis revealed that longer relative phase 2 digestion time (the interval from the start of collection to its end) and higher North American Islet Donor Scores were associated with higher islet yield. These findings highlight the importance of donor anthropometrics, procedural consistency, and thermal regulation during islet isolation. Optimizing donor selection and controlling intra-procedural variables can improve islet yield and increase the likelihood of achieving the required clinical transplantation islet dose.

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