Islet assessment for transplantation.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Papas
Klearchos K
KK
Department of Surgery, Schulze Diabetes Institute, University of Minnesota, Minneapolis, 55455, USA. papas006@umn.edu
Suszynski
Thomas M
TM
Colton
Clark K
CK
D000818:Animals; D001681:Biological Assay / Q000592:standards; D002470:Cell Survival; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D004195:Disease Models, Animal; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D016381:Islets of Langerhans Transplantation / Q000592:standards; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D010101:Oxygen Consumption; D011786:Quality Control; D015203:Reproducibility of Results; D020858:Tissue and Organ Harvesting / Q000592:standards; D016896:Treatment Outcome