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Longitudinal In Vivo Imaging and Quantification of Human Pancreatic Islet Grafting and Contributing Host Cells in the Anterior Eye Chamber
Published on: June 11, 2020
Human islets derived from donors after cardiac death are fully biofunctional
1Diabetes Research Group, King's College London School of Medicine, London, UK.
Summary
Islets from non-heart-beating donors (NHBDs) offer a promising alternative for Type 1 diabetes treatment, yielding more islet equivalents than brain-dead donors (BDDs) with comparable viability. NHBD islets are suitable for clinical use when warm ischemia time is limited.
Area of Science:
- Transplantation immunology
- Endocrinology
- Regenerative medicine
Background:
- Type 1 diabetes treatment relies on islet transplantation, but donor limitations hinder widespread application.
- Brain-dead donors (BDDs) are the primary source of islets, yet donor numbers and long-term islet survival remain critical challenges.
- Non-heart-beating donors (NHBDs) present a potential alternative source of islets due to potentially lower circulating cytokine levels.
Purpose of the Study:
- To evaluate the clinical feasibility of using islets from non-heart-beating donors (NHBDs) compared to islets from brain-dead donors (BDDs) for Type 1 diabetes treatment.
- To assess the quantity, quality, and functional outcomes of islets isolated from NHBDs versus BDDs.
- To determine the impact of warm ischemia time (WIT) on islet function and suitability for transplantation.
Main Methods:
- Comparative analysis of islets isolated from 10 NHBDs and 12 BDDs over a defined period.
- Quantification of islet yield using islet equivalent number (IEQ) per pancreas.
- Assessment of islet viability, ATP and GTP content, and in vivo function in diabetic mouse models.
Main Results:
- NHBDs yielded significantly more islets (approximately 12.6% higher IEQ/pancreas) compared to BDDs (p=0.01).
- Islet viability was comparable between NHBDs and BDDs.
- Lower ATP and GTP content in NHBD islets correlated negatively with warm ischemia time (WIT).
- NHBD islets demonstrated a longer onset of hyperglycemia control in mice but sustained euglycemia equally well as BDD islets.
Conclusions:
- Islets from NHBDs are a viable source for Type 1 diabetes treatment, offering increased yield compared to BDDs.
- NHBD islets are clinically suitable, particularly when warm ischemia time is less than or equal to 25 minutes.
- Further research into optimizing islet isolation and preservation from NHBDs could expand donor availability and improve transplant outcomes.
