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

Area of Science:

• Transplantation immunology
• Islet cell biology
• Surgical innovation

Background:

• Human islet isolation is critical for treating type 1 diabetes.
• Maximizing islet yield is essential for successful transplantation outcomes.
• Identifying factors influencing islet yield is crucial for procedural optimization.

Purpose of the Study:

• To investigate donor and procedural variables affecting human islet yield.
• To identify predictors of successful islet isolation for transplantation.
• To compare procedural differences between clinical and research isolations.

Main Methods:

• Retrospective analysis of 133 human islet isolations over 15 years.
• Stratification of isolations by islet yield (≥400,000 IEQ vs. <400,000 IEQ).
• Logistic regression modeling to predict isolation success based on donor and procedural factors.

Main Results:

• Higher donor BMI and height (>170 cm) correlated with successful isolation.
• Enzyme perfusion temperature >14°C for >50% of duration was a risk factor for failure.
• Clinical isolations showed better thermal control, higher digestion efficiency, and less undigested tissue.
• A model using body surface area, packed tissue volume, and Phase 1 digestion time predicted success (AUC=0.755).
• Longer Phase 2 digestion time and higher North American Islet Donor Scores increased islet yield.

Conclusions:

• Donor anthropometrics (BMI, height) and procedural consistency are vital for islet yield.
• Strict thermal regulation during enzyme perfusion is critical to prevent isolation failure.
• Optimizing donor selection and intra-procedural variables enhances islet yield for clinical transplantation.