Pancreatic islet transplantation

Abstract

Background: No formulation of exogenous insulin available to date has yet been able to mimic the physiological nictemeral rhythms of this hormone, and despite all engineering advancements, the theoretical proposal of developing a mechanical replacement for pancreatic β cell still has not been reached. Thus, the replacement of β cells through pancreas and pancreatic islet transplantation are the only concrete alternatives for re-establishing the endogenous insulin secretion in type 1 diabetic patients. Since only 1 to 1.5% of the pancreatic mass corresponds to endocrine tissue, pancreatic islets transplantation arises as a natural alternative. Data from the International Islet Transplant Registry (ITR) from 1983 to December 2000 document a total of 493 transplants performed around the world, with progressively worse rates of post-transplant insulin independence. In 2000, the "Edmonton Protocol" introduced several modifications to the transplantation procedure, such as the use of a steroid-free immunosuppression regimen and transplantation of a mean islet mass of 11,000 islet equivalents per kilogram, which significantly improved 1-year outcomes. Although the results of a 5-year follow-up in 65 patients demonstrated improvement in glycemic instability in a significant portion of them, only 7.5% of the patients have reached insulin independence, indicating the need of further advances in the preservation of the function of transplanted islet. In addition to the scarcity of organs available for transplantation, islets transplantation still faces major challenges, specially those related to cell loss during the process of islet isolation and the losses related to the graft site, apoptosis, allorejection, autoimmunity, and immunosuppression. The main strategies to optimize islet transplantation aim at improving all these aspects.

Human pancreatic islet transplantation: an update and description of the establishment of a pancreatic islet isolation laboratory

“…The process of islet isolation involves the extraction of insulin-producing cells from the pancreas, while preserving their structural and functional integrity (30). Islet isolation methods have become increasingly sophisticated over the past three decades (7) and advances in this area are at least partly attributable to the use of a semi-automated method of controlled pancreatic digestion developed by Camillo Ricordi in 1989 (19).…”

“…Donor characteristics (age, gender, medical history, body mass index [BMI], cause of death, use of vasopressor agents) and pancreas characteristics (size, fat content, duration of cold ischemia) may also influence the quality and quantity of the isolated islets (30,50,51). Although organs donated by individuals with BMI > 25 kg/m 2 and/or age over 50 years tend to produce a greater number of islets, these islets do not always function adequately (50,51).…”

“…The duration of cold ischemia is also relevant to the islet isolation process, since increased cold ischemia time may damage the pancreatic tissue. Therefore, the type of solution used to preserve the pancreas and decrease the deleterious effects of hypoxia may have an important effect on transplant results (30). Most isolation procedures involve the use of the UW (University of Wisconsin) solution, which contains electrolytes and other substances that contribute to cell integrity (30).…”

“…Therefore, the type of solution used to preserve the pancreas and decrease the deleterious effects of hypoxia may have an important effect on transplant results (30). Most isolation procedures involve the use of the UW (University of Wisconsin) solution, which contains electrolytes and other substances that contribute to cell integrity (30). However, some studies have found that the combined use of UW solution and other substances with high oxygen affinity (two-layer perfluorocarbon method) led to improved pancreatic preservation (54,55), although these results were most pronounced in cases of prolonged cold ischemia (56).…”

Metilglioxal: uma toxina endógena?

“…8,9 Por isso, ainda não há uma forma eficaz de tratamento da doença, 10 mas o transplante de ilhotas é vislumbrado como uma das alternativas. 11 O primeiro transplante de ilhotas no Brasil foi realizado na cidade de São Paulo, pelo Hospital Albert Einstein, com a colaboração da Profa. Dra.…”