Journal
CURRENT OPINION IN ORGAN TRANSPLANTATION
Volume 14, Issue 6, Pages 674-682Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOT.0b013e328332a489
Keywords
marginal mass; oxygen consumption rate; potency; purity; release criteria; viability
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Funding
- NCRR NIH HHS [U42 RR016598-07, U42 RR016598-08, U42 RR016598, U42 RR 016598-01] Funding Source: Medline
- NIDDK NIH HHS [R01 DK063108, R01-DK063108-01A1] Funding Source: Medline
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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.
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