Islet assessment for transplantation

Curr Opin Organ Transplant. 2009 Dec;14(6):674-82. doi: 10.1097/MOT.0b013e328332a489.

Abstract

Purpose of review: There is a critical need for meaningful viability and potency assays that characterize islet preparations for release prior to clinical islet cell transplantation. Development, testing, and validation of such assays have been the subject of intense investigation for the last decade. These efforts are reviewed, highlighting the most recent results while focusing on the most promising assays.

Recent findings: Assays based on membrane integrity do not reflect true viability when applied to either intact islets or dispersed islet cells. Assays requiring disaggregation of intact islets into individual cells for assessment introduce additional problems of cell damage and loss. Assays evaluating mitochondrial function, specifically mitochondrial membrane potential, bioenergetic status, and cellular oxygen consumption rate, especially when conducted with intact islets, appear most promising in evaluating their quality prior to islet cell transplantation. Prospective, quantitative assays based on measurements of oxygen consumption rate with intact islets have been developed, validated, and their results correlated with transplant outcomes in the diabetic nude mouse bioassay.

Conclusion: More sensitive and reliable islet viability and potency tests have been recently developed and tested. Those evaluating mitochondrial function are most promising, correlate with transplant outcomes in mice, and are currently being evaluated in the clinical setting.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Assay* / standards
  • Cell Survival
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / surgery*
  • Disease Models, Animal
  • Humans
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology*
  • Islets of Langerhans Transplantation* / standards
  • Membrane Potential, Mitochondrial
  • Mice
  • Mitochondria / metabolism
  • Oxygen Consumption
  • Quality Control
  • Reproducibility of Results
  • Tissue and Organ Harvesting* / standards
  • Treatment Outcome