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.
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.
Authors: D G Pipeleers; M Pipeleers-Marichal; J C Hannaert; M Berghmans; P A In't Veld; J Rozing; M Van de Winkel; W Gepts Journal: Diabetes Date: 1991-07 Impact factor: 9.461
Authors: Anna Pisania; Gordon C Weir; John J O'Neil; Abdulkadir Omer; Vaja Tchipashvili; Ji Lei; Clark K Colton; Susan Bonner-Weir Journal: Lab Invest Date: 2010-08-09 Impact factor: 5.662
Authors: Romie F Gibly; Xiaomin Zhang; Melanie L Graham; Bernhard J Hering; Dixon B Kaufman; William L Lowe; Lonnie D Shea Journal: Biomaterials Date: 2011-09-28 Impact factor: 12.479
Authors: Stephen T Bartlett; James F Markmann; Paul Johnson; Olle Korsgren; Bernhard J Hering; David Scharp; Thomas W H Kay; Jonathan Bromberg; Jon S Odorico; Gordon C Weir; Nancy Bridges; Raja Kandaswamy; Peter Stock; Peter Friend; Mitsukazu Gotoh; David K C Cooper; Chung-Gyu Park; Phillip OʼConnell; Cherie Stabler; Shinichi Matsumoto; Barbara Ludwig; Pratik Choudhary; Boris Kovatchev; Michael R Rickels; Megan Sykes; Kathryn Wood; Kristy Kraemer; Albert Hwa; Edward Stanley; Camillo Ricordi; Mark Zimmerman; Julia Greenstein; Eduard Montanya; Timo Otonkoski Journal: Transplantation Date: 2016-02 Impact factor: 4.939
Authors: Amy C Kelly; Kate E Smith; William G Purvis; Catherine G Min; Craig S Weber; Amanda M Cooksey; Craig Hasilo; Steven Paraskevas; Thomas M Suszynski; Bradley P Weegman; Miranda J Anderson; Leticia E Camacho; Robert C Harland; Thomas Loudovaris; Jana Jandova; Diana S Molano; Nicholas D Price; Ivan G Georgiev; William E Scott; Derek M D Manas; James A M Shaw; Doug OʼGorman; Tatsuya Kin; Fiona M McCarthy; Gregory L Szot; Andrew M Posselt; Peter G Stock; Theodore Karatzas; A M James Shapiro; Ronald M Lynch; Sean W Limesand; Klearchos K Papas Journal: Transplantation Date: 2019-01 Impact factor: 4.939
Authors: Kate R Mueller; A N Balamurugan; Gary W Cline; Rebecca L Pongratz; Rebecca L Hooper; Bradley P Weegman; Jennifer P Kitzmann; Michael J Taylor; Melanie L Graham; Henk-Jan Schuurman; Klearchos K Papas Journal: Xenotransplantation Date: 2013-02-05 Impact factor: 3.907
Authors: Gopalakrishnan Loganathan; Melanie L Graham; David M Radosevich; Sajjad M Soltani; Mukesh Tiwari; Takayuki Anazawa; Klearchos K Papas; David E R Sutherland; Bernhard J Hering; A N Balamurugan Journal: Transplantation Date: 2013-06-27 Impact factor: 4.939
Authors: Klearchos K Papas; Theodore Karatzas; Thierry Berney; Thomas Minor; Paris Pappas; François Pattou; James Shaw; Christian Toso; Henk-Jan Schuurman Journal: Clin Transplant Date: 2013-01-18 Impact factor: 2.863