TY - JOUR
T1 - Islet assessment for transplantation
AU - Papas, Klearchos K.
AU - Suszynski, Thomas M.
AU - Colton, Clark K.
PY - 2009/12
Y1 - 2009/12
N2 - 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 findings: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.
AB - 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 findings: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.
KW - Marginal mass
KW - Oxygen consumption rate
KW - Potency
KW - Purity
KW - Release criteria
KW - Viability
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U2 - 10.1097/MOT.0b013e328332a489
DO - 10.1097/MOT.0b013e328332a489
M3 - Review article
C2 - 19812494
AN - SCOPUS:74349099562
SN - 1087-2418
VL - 14
SP - 674
EP - 682
JO - Current Opinion in Organ Transplantation
JF - Current Opinion in Organ Transplantation
IS - 6
ER -