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Invited Speakers and Oral Abstracts of the 2009 Joint Meeting of the International Pancreas and Islet Transplant Association (IPITA) and the International Xenotransplantation Association (IXA)
Author(s) -
Masayuki Shimoda,
Hirofumi Noguchi,
Bashoo Naziruddin,
Yasutaka Fujita,
Daisuke Chujo,
Morihito Takita,
Han Peng,
Yoshiko Tamura,
Greg Olsen,
Koji,
Sugimoto,
Takeshi Itoh,
Nicholas Onaca,
Marlon F Levy,
Paul A Grayburn,
Shinichi Matsumoto
Publication year - 2009
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.2009.00539_2.x
Subject(s) - xenotransplantation , islet , medicine , association (psychology) , pancreas , transplantation , psychology , insulin , psychotherapist
Islet transplantation is emerging as a promising treatment option for qualified patients with Type 1 Diabetes. Inconsistent isolation, purification, and recovery of large numbers of high quality islets remain substantial impediments to progress in the field. Donor brain death, pancreas procurement and preservation, islet isolation, purification and culture can have a synergistic and detrimental effect on islet isolation and engraftment. Current cold preservation protocols, including the two layer method, do not prevent exposure of the majority of the human pancreas to hypoxia. Existing islet isolation and purification protocols amplify the impact of cold ischemia, with exposure of the islets to proteolytic enzymes, mechanical stress, warm ischemia and reactive oxygen intermediates. Islet culture may further expose islets to hypoxia. The absence of reliable tools for the objective assessment of pancreas and islet quality has further hindered progress. The recent development of tools for the real-time, reliable assessment of pancreas and islet quality (such as assays based on NMR and oxygen consumption rate) is expected to accelerate progress by enabling the objective evaluation of emerging approaches aimed at maximizing viable islet yield per pancreas. These approaches include: (1) pancreas preservation protocols based on liquid or gas perfusion that may minimize exposure to hypoxia, prevent autolysis, and mechanically facilitate islet liberation from the pancreatic mass; (2) use of anti-apoptotic agents (such as JNK inhibitors and antioxidants) either during organ preservation but also during islet isolation and culture to inhibit the activation of proapoptotic pathways; (3) improved oxygenation, temperature and pH control during pancreas digestion and islet processing to minimize islet stress; (4) removing islets as soon as they are liberated from the pancreatic tissue mass during isolation and circumventing the need for density gradient purification by magnetic retraction using continuous flow sorters to minimize exposure to proteolytic enzymes and other isolation and purification stresses; (5) culture islets in specially designed gas permeable vessels using enhanced media formulations and extend islet culture (7 days), to maintain the amount of viable islet tissue in a preparation, reduce the amount of dead tissue, reduce immunogenicity and provide a ‘‘calming’’ environment for the islet product prior to transplantation. The approaches outlined above and their implications in islet preservation and preconditioning prior to transplantation will be discussed.