Islet isolation assessment in man and large animals.
Camillo Ricordi,Camillo Ricordi,Derek W. R. Gray,Bernhard J. Hering,Dixon B. Kaufman,Garth L. Warnock,Norman M. Kneteman,S. P. Lake,Nicholas J.M. London,Carlo Socci,Rodolfo Alejandro,Y. Zeng,David W. Scharp,Giorgio Luciano Viviani,L. Falqui,Andreas G. Tzakis,Reinhard G. Bretzel,Konrad Federlin,Guido Pozza,Roger F.L. James,Ray V. Rajotte,Valerio Di Carlo,Peter J. Morris,David E.R. Sutherland,Thomas E. Starzl,Daniel H. Mintz,Paul E. Lacy +26 more
- Vol. 27, Iss: 3, pp 185-195
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TLDR
These general guidelines will be of assistance to standardize the assessment of islet isolations, making it possible to better interpret and compare procedures from different centers.Abstract:
Recent progress in islet isolation from the pancreas of large mammals including man, accentuated the need for the development of precise and reproducible techniques to assess islet yield. In this report both quantitative and qualitative criteria for islet isolation assessment were discussed, the main topics being the determination of number, volume, purity, morphologic integrity andin vitro andin vivo function tests of the final islet preparations. It has been recommended that dithizone should be used as a specific stain for immediate detection of islet tissue making it possible to estimate both the total number of islets (dividing them into classes of 50 µ diameter range increments) and the purity of the final preparation. Appropriate morphological assessment should include confirmation of islet identification, assessment of the morphological integrity and of the purity of the islet preparation. The use of fluorometric inclusion and exclusion dyes together have been suggested as a viability assay to simultaneously quantitate the proportion of cells that are intact or damaged. Perifusion of islets with glucose provides a dynamic profile of glucose-mediated insulin release and of the ability of the cells to down regulate insulin secretion after the glycemic challenge is interrupted. Although perifusion data provides a useful guide to islet viability the quantity and kinetics of insulin release do not necessarily predict islet performance after implantation. Therefore, the ultimate test of islet viability is their function after transplantation into a diabetic recipient. For this reason,in vivo models of transplantation of an aliquot of the final islet preparation into diabetic nude (athymic) rodents have been suggested. We hope that these general guidelines will be of assistance to standardize the assessment of islet isolations, making it possible to better interpret and compare procedures from different centers.read more
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Journal ArticleDOI
Islet Transplantation in Seven Patients with Type 1 Diabetes Mellitus Using a Glucocorticoid-Free Immunosuppressive Regimen
A. M. J. Shapiro,Jonathan R. T. Lakey,Edmond A. Ryan,Gregory S. Korbutt,Ellen L. Toth,Garth L. Warnock,Norman M. Kneteman,Ray V. Rajotte +7 more
TL;DR: The observations in patients with type 1 diabetes indicate that islet transplantation can result in insulin independence with excellent metabolic control when glucocorticoid-free immunosuppression is combined with the infusion of an adequate islet mass.
Journal ArticleDOI
Five-Year Follow-Up After Clinical Islet Transplantation
Edmond A. Ryan,Breay W. Paty,Peter A. Senior,David L. Bigam,Eman Alfadhli,Norman M. Kneteman,Jonathan R. T. Lakey,A. M. James Shapiro +7 more
TL;DR: In conclusion, islet transplantation can relieve glucose instability and problems with hypoglycemia and point to the need for further progress in the availability of transplantable islets, improving islet engraftment, preserving islet function, and reducing toxic immunosuppression.
Journal ArticleDOI
Clinical Outcomes and Insulin Secretion After Islet Transplantation With the Edmonton Protocol
Edmond A. Ryan,Jonathan R. T. Lakey,Ray V. Rajotte,Gregory S. Korbutt,Tatsuya Kin,Sharleen Imes,Alex Rabinovitch,John F. Elliott,David L. Bigam,Norman M. Kneteman,Garth L. Warnock,Ingrid Larsen,A. M. J. Shapiro +12 more
TL;DR: Islet transplantation has successfully corrected labile type 1 diabetes and problems with hypoglycemia, and the results show persistent insulin secretion, which is consistent with good glycemic control.
Journal ArticleDOI
Successful islet transplantation: continued insulin reserve provides long-term glycemic control.
Edmond A. Ryan,Jonathan R. T. Lakey,Breay W. Paty,Sharleen Imes,Gregory S. Korbutt,Norman M. Kneteman,David L. Bigam,Ray V. Rajotte,A. M. James Shapiro +8 more
TL;DR: The results indicate that prolonged insulin independence can be achieved after islet transplantation, and there are some risks associated acutely with the procedure, and hypercholesterolemia and hypertension are treatable concerns on longer-term follow-up.
Journal ArticleDOI
Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates
Omid Veiseh,Joshua C. Doloff,Minglin Ma,Arturo J. Vegas,Hok Hei Tam,Andrew Bader,Jie Li,Erin Langan,Jeffrey Wyckoff,Whitney S. Loo,Siddharth Jhunjhunwala,Alan Chiu,Sean M. Siebert,Katherine Tang,Jennifer Hollister-Lock,Stephanie Aresta-Dasilva,Matthew A. Bochenek,Joshua E. Mendoza-Elias,Yong Wang,Merigeng Qi,Danya M. Lavin,Michael Chen,Nimit Dholakia,Raj Thakrar,Igor Lacík,Gordon C. Weir,Jose Oberholzer,Dale L. Greiner,Robert Langer,Daniel G. Anderson +29 more
TL;DR: In this paper, a broad variety of material classes significantly abrogate foreign body reactions and fibrosis in rodent and non-human primates when the spheres are larger than 1.5 mm in diameter.
References
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Journal ArticleDOI
Method for the Isolation of Intact Islets of Langerhans from the Rat Pancreas
Paul E. Lacy,Mery Kostianovsky +1 more
TL;DR: A simple method for the isolation of intact islets from the normal rat pancreas is described, based upon disruption of the acinar parenchyma by injecting Hanks solution into the pancreatic duct system followed by incubation of the Pancreas in collagenase.
Journal ArticleDOI
Immunoassay of Insulin: Two Antibody System: Plasma Insulin Levels of Normal, Subdiabetic and Diabetic Rats
Carl R Morgan,Arnold Lazarow +1 more
TL;DR: A two antibody system of insulin assay for immunoassay of insulin induces the production of specific nonprecipitating antibodies, both in experimental animals and in humans.
Journal ArticleDOI
Automated Method for Isolation of Human Pancreatic Islets
TL;DR: An automated method for the isolation of human pancreatic islets meets the following requirements: minimal traumatic action on the islets, continuous digestion in which the islet that are progressively liberated can be saved from further enzymatic action, high yield and purity of the isolated islets.
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