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Regenerative medicine
Published in Julie Kent, Regenerating Bodies, 2012
Since 2000, when the first islet transplants using cells from cadaver pancreas were performed using the ‘Edmonton protocol’, the possibility of treating diabetes with SC transplants has received greater attention. However, the scientists were seen as ‘dampening down expectations’ about the prospects of SC therapies for the treatment of diabetes. This was linked to problems of controlling embryonic SC growth and preventing the formation of tumours; problems associated with genetic modification to create insulin-producing beta cells and prevent immune rejection of implanted cells; and problems relating to the transferability of animal studies to human therapies. Accordingly, the authors concluded: Our scientists see the target of ES-driven cell therapies as something that may be unachievable, except in very specific and limited areas. In contrast, they see the prospects for significant scientific breakthroughs from SCs in understanding basic cell and developmental biology as achievable. Perhaps there is a shift here, with some scientists now specify -ing expectations around SCs as scientific tools rather than medical therapies.(Wainwright et al. 2006b:2061)
Cellular and Molecular Imaging of the Diabetic Pancreas
Published in Michel M. J. Modo, Jeff W. M. Bulte, Molecular and Cellular MR Imaging, 2007
Islet transplantation has emerged as one of the most promising new treatments for diabetes. The earliest reports of islet transplantation in animal models appeared in 1972.130 The first clinical islet allograft was performed in 1974.131 Over the next 25 years, numerous attempts were made to achieve normoglycemia in type 1 diabetic patients using islet transplantation, with limited success. Although some functionality was achieved, as evidenced by C-peptide, the majority of cases failed to demonstrate insulin independence or long-term engraftment.131 With the development in 1999 of an improved protocol for islet transplantation by a group from the University of Alberta, it became possible to attain reproducible success in terms of insulin independence through islet transplantation.132 The success of this new protocol, named the Edmonton protocol, rests mainly on enhanced immunosupression treatment compared to previous protocols and on the improved islet delivery strategy, namely, intraportal infusion of freshly isolated islets, followed by a second or third infusion of additional islets.131
Pathophysiology and Clinical Management of Diabetes and Prediabetes
Published in Jeffrey I. Mechanick, Elise M. Brett, Nutritional Strategies for the Diabetic & Prediabetic Patient, 2006
Elliot J. Rayfield, Marilyn V. Valentine
Whole pancreas transplants have successfully restored insulin secretion in people with advanced diabetes but are usually limited to those who are also undergoing kidney transplantation [114]. In 2000, Shapiro et al. [115] developed the Edmonton Protocol for islet transplantation, which used a larger quantity of islet cells with drugs that were less toxic to the immune system. This method infuses islet cells through a small tube into the portal vein of the liver. Patients whose islet cells fail to continue secreting insulin can be retransplanted. Islet cell transplants are still experimental and are available to people who are willing to participate in a study protocol. Also, only a small percentage of islet cell transplant recipients achieve normal blood glucose levels. It is unclear whether a transplant can stop or reverse secondary complications related to diabetes. It is also unclear whether islet cell transplantation will ultimately extend a patent’s long-term survival.
Tissue engineering approaches and generation of insulin-producing cells to treat type 1 diabetes
Published in Journal of Drug Targeting, 2023
Mozafar Khazaei, Fatemeh Khazaei, Elham Niromand, Elham Ghanbari
Islet transplantation using the Edmonton protocol provides an option for individuals who are resistant to exogenous insulin injection [5]. This method includes clinical isolation of human islet from cadaveric donors, intra-portal transplantation of islet cells and a glucocorticoid-free immunosuppressive treatment for the patient following transplantation. Therefore, patients with T1D can stabilise the blood glucose and maintain the generation of endogenous insulin with this transplant [6]. The shortage of suitable donor organ, immunological rejection and the long-term use of immunosuppressive therapy have been identified as obstacles to implementing the Edmonton protocol [7,8]. In spite of advancements in the isolation and cell culture protocols, as well as the utilisation of different implantation sites for the β-cells, only 60%–85% of patients remain insulin-independent one year after transplantation, and this percentage declines with time so that around 20% of patients remain independent after five years [9].
An overview of current advancements in pancreatic islet transplantation into the omentum
Published in Islets, 2021
Kimia Damyar, Vesta Farahmand, David Whaley, Michael Alexander, Jonathan R. T. Lakey
Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder in which insulin-producing β-cells, predominant within the islets of Langerhans in the pancreas, are destroyed. This ultimately results in blood sugar elevation and loss of glycemic control.1 The development of the Edmonton protocol in 2000 introduced islet transplantation as a method to restore glycemic control in insulin-dependent T1DM patients.2 Under the current standard of care, the liver is considered the primary site for clinical islet transplantation. The islets can be easily infused into the hepatic portal system allowing β-cells to effectively restore glycemic control to the patients. However, there are limitations associated with islet infusion into the portal system. There is a risk of portal vein thrombosis as well as the elevation of portal pressure that can lead to uncontrolled bleeding. Moreover, there is a possibility of islet loss after transplantation due to the IBMIR that can occur when islets encounter the recipient’s blood.3–6 In order to address the limitations associated with intrahepatic islet transplantation, alternative sites have been investigated including but not limited to the omentum, peritoneum, spleen, renal subcapsule, and gastric submucosa. However, some of these sites show limitations in capacity and functional outcome or introduce further complications post-transplant.3,7–12
Over ten-year insulin independence following single allogeneic islet transplant without T-cell depleting antibody induction
Published in Islets, 2018
Jack Williams, Nicholas Jacus, Kevin Kavalackal, Kirstie K. Danielson, Rebecca S. Monson, Yong Wang, Jose Oberholzer
In 2000, Shapiro et al. reported improvement in the efficacy of islet transplantation as a functional cure for type 1 diabetes (T1D) using the Edmonton Protocol, which involved standardizing islet cell isolation procedures, the number (dose) of transplanted islets, and the use of steroid-free immunosuppression.1 However, only 1 of the 36 recipients from the International Trial of the Edmonton Protocol remained insulin independent after three years.2 With continuing progress in both islet isolation and clinical management after transplant, the rate of insulin independence following islet transplantation has steadily improved. For patients transplanted between 2007 and 2010, 44% were insulin independent at three years.3 More recently, our research group demonstrated that 60% of patients remained insulin independent at five years, without the use of T-cell depleting antibody induction immunosuppression.4 Despite these improvements, in a substantial number of cases, islet cell transplantation is still followed by a gradual decrease in the production of insulin and partial (to complete) graft loss.5 Long-term maintenance of islet graft function will be central to islet transplantation becoming a viable treatment option for T1D patients.