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islet cell auto transplantation

Cornelis R van der Torren, Jessica S Suwandi, DaHae Lee, Ernst-Jan T van 't Wout, Gaby Duinkerken, Godelieve Swings, Arend Mulder, Frans H J Claas, Zhidong Ling, Pieter Gillard, Bart Keymeulen, Peter In 't Veld, Bart O Roep
Transplantation of islet allografts into type 1 diabetic recipients usually requires multiple pancreas donors to achieve insulin independence. This adds to the challenges of immunological monitoring of islet transplantation currently relying on surrogate immune markers in peripheral blood. We investigated donor origin and infiltration of islets transplanted in the liver of a T1D patient who died of hemorrhagic stroke four months after successful transplantation with two intraportal islet grafts combining six donors...
October 10, 2016: Cell Transplantation
Sofie De Groef, Willem Staels, Naomi Van Gassen, Marie Lemper, Yixing Yuchi, Mozhdeh Sojoodi, Leen Bussche, Yves Heremans, Gunter Leuckx, Nico De Leu, Mark Van de Casteele, Luc Baeyens, Harry Heimberg
The generation of beta(-like) cells to compensate for their absolute or relative shortage in type 1 and type 2 diabetes is an obvious therapeutic strategy. Patients first received grafts of donor islet cells over 25 years ago, but this procedure has not become routine in clinical practice because of a donor cell shortage and (auto)immune problems. Transplantation of differentiated embryonic and induced pluripotent stem cells may overcome some but not all the current limitations. Reprogramming exocrine cells towards functional beta(-like) cells would offer an alternative abundant and autologous source of beta(-like) cells...
September 2016: Diabetologia
Edgardo D Rivera Rivera, Ankur Chugh, Jonathon Cordova, Sona Young
A 13-year-old boy with a strong family history of hereditary pancreatitis was found to have a PRSS1 mutation after being tested at age 5 years during his first documented incident of pancreatitis. Since then, a multidisciplinary team has been treating him for the diagnosis of hereditary pancreatitis. His pain episodes increased in severity over the past several months such that the pain began to severely interfere with his daily life. After extensive discussion, a total pancreatectomy with auto islet cell transplant was performed...
February 2016: Pediatric Annals
Massimo Venturini, Paola Maffi, Giulia Querques, Giulia Agostini, Lorenzo Piemonti, Sandro Sironi, Francesco De Cobelli, Paolo Fiorina, Antonio Secchi, Alessandro Del Maschio
Percutaneous intra-portal islet transplantation (PIPIT) is a less invasive, safer, and repeatable therapeutic option for brittle type 1 diabetes, compared to surgical pancreas transplantation. Hepatic steatosis is a consequence of the islet engraftment but it is curiously present in a limited number of patients and its meaning is controversial. The aims of this study were to assess hepatic steatosis at ultrasound (US) after PIPIT investigating its relationship with graft function and its role in predicting the clinical outcome...
August 2015: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Michal Radomski, Amer H Zureikat
Chronic pancreatitis is a challenging disease; the constellation of chronic abdominal pain and metabolic derangements present unique difficulties to the treating physician. Initial treatment revolves around lifestyle modification, pain control, and management of exocrine insufficiency. In refractory cases, total pancreatectomy with islet cell auto transplantation (TP-IAT) is an option for patients with diffuse disease not amenable to subtotal pancreatectomy or a decompressive (drainage) operation. This procedure aspires to alleviate pain and avoid surgically induced brittle diabetes, a morbid complication of total pancreatectomy alone...
January 2015: JOP: Journal of the Pancreas
Annika C Sun, Dawei Ou, Dan S Luciani, Garth L Warnock
Auto- and alloreactive T cells are major culprits that damage β-cells in type 1 diabetes (T1D) and islet transplantation. Current immunosuppressive drugs can alleviate immune-mediated attacks on islets. T cell co-stimulation blockade has shown great promise in autoimmunity and transplantation as it solely targets activated T cells, and therefore avoids toxicity of current immunosuppressive drugs. An attractive approach is offered by the newly-identified negative T cell co-signaling molecule B7-H4 which is expressed in normal human islets, and its expression co-localizes with insulin...
December 15, 2014: World Journal of Diabetes
Nathan W Zammit, Shane T Grey
A20 is most characteristically described in terms relating to inflammation and inflammatory pathologies. The emerging understanding of inflammation in the etiology of diabetes mellitus lays the framework for considering a central role for A20 in this disease process. Diabetes mellitus is considered a major health issue, and describes a group of common metabolic disorders pathophysiologically characterized by hyperglycemia. Within islets of Langherhans, the endocrine powerhouse of the pancreas, are the insulin-producing pancreatic beta-cells...
2014: Advances in Experimental Medicine and Biology
Noaman S Ali, R Matthew Walsh
Chronic pancreatitis is the result of irreversible damage to pancreatic acinar cells, and can result in debilitating chronic pain for patients. Treatment centers on pain relief, often with chronic narcotic use. Surgical therapy consists of both resection procedures to remove affected pancreatic parenchyma and drainage procedures to facilitate drainage of the main pancreatic duct. Total pancreatectomy historically was utilized in extreme cases due to the brittle glucose control that followed from the total loss of islet cells...
September 2014: Current Treatment Options in Gastroenterology
Amer H Zureikat, Trang Nguyen, Brian A Boone, Martin Wijkstrom, Melissa E Hogg, Abhinav Humar, Herbert Zeh
BACKGROUND: Total pancreatectomy (TP) is a morbid but sometimes necessary operation. Robotic TP is not often reported but may harbor some advantages compared to the open approach. This manuscript details a single institution's outcomes and technique of robotic TP. An accompanying video demonstrates a robotic TP with auto islet cell transplantation (IAT) in which (1) the arterial blood supply and venous drainage are kept intact until the last step of the TP to minimize warm ischemia time and (2) extirpation of the entire pancreas is performed without dividing the pancreatic neck to maximize islet recovery...
January 2015: Surgical Endoscopy
Srinath Chinnakotla, David M Radosevich, Ty B Dunn, Melena D Bellin, Martin L Freeman, Sarah J Schwarzenberg, A N Balamurugan, Josh Wilhelm, Barbara Bland, Selwyn M Vickers, Gregory J Beilman, David E R Sutherland, Timothy L Pruett
BACKGROUND: Chronic pancreatitis is a debilitating disease resulting from many causes. The subset with hereditary/genetic pancreatitis (HGP) not only has chronic pain, but also an increased risk for pancreatic cancer. Long-term outcomes of total pancreatectomy (TP) and islet autogeneic transplantation (IAT) for chronic pancreatitis due to HGP are not clear. STUDY DESIGN: We reviewed a prospectively maintained database of 484 TP-IATs from 1977 to 2012 at a single center...
April 2014: Journal of the American College of Surgeons
Neil H Bhayani, Laura M Enomoto, Jennifer L Miller, Gail Ortenzi, Jussuf T Kaifi, Eric T Kimchi, Kevin F Staveley-O'Carroll, Niraj J Gusani
BACKGROUND: In pancreatitis, total pancreatectomy (TP) is an effective treatment for refractory pain. Islet cell auto-transplantation (IAT) may mitigate resulting endocrinopathy. Short-term morbidity data for TP + IAT and comparisons with TP are limited. METHODS: This study, using 2005-2011 National Surgical Quality Improvement Program data, examined patients with pancreatitis or benign neoplasms. Morbidity after TP alone was compared with that after TP + IAT. RESULTS: In 126 patients (40%) undergoing TP and 191 (60%) patients undergoing TP + IAT, the most common diagnosis was chronic pancreatitis...
June 2014: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
J R F Abreu, B O Roep
Type 1 diabetes (T1D) is an autoimmune disease in which the insulin-producing beta-cells are destroyed. Islet or pancreas transplantation can restore insulin secretion and are established therapies for subgroups of T1D patients. Long-term insulin-independence is, however, hampered by recurrent autoimmunity and rejection. Accurate monitoring of these immune events is therefore of critical relevance for the timely detection of deleterious immune responses. The identification of relevant immune biomarkers of allo- and autoreactivity has allowed a more accurate monitoring of disease progression and responses to therapy at early stages, allowing proper therapeutic intervention, and possibly improvements in the success rate of islet and pancreas transplantation...
October 2013: Current Diabetes Reports
Aini Xie, Eric Dale Buras, Jiahong Xia, Wenhao Chen
Since its discovery in 2000, IL-21 has been shown to play critical roles in the regulation of both innate and adaptive immune responses. IL-21 is produced predominantly by multiple effector CD4(+) T-cell types [T helper 17 (Th17), follicular helper T (TFH), and other activated CD4(+) cells] and NKT cells. In addition to T cell receptor (TCR) signals, the production of IL-21 by activated CD4(+) T cells is intricately regulated by various extrinsic factors and intrinsic molecules, such as IL-6, IL-21, ICOS, Stat3, IRF4, and Batf...
August 24, 2012: Journal of Clinical & Cellular Immunology
A M James Shapiro
Remarkable progress has been made in islet transplantation over a span of 40 years. Once just an experimental curiosity in mice, this therapy has moved forward, and can now provide robust therapy for highly selected patients with type 1 diabetes (T1D), refractory to stabilization by other means. This progress could not have occurred without extensive dynamic international collaboration. Currently, 1,085 patients have undergone islet transplantation at 40 international sites since the Edmonton Protocol was reported in 2000 (752 allografts, 333 autografts), according to the Collaborative Islet Transplant Registry...
2012: Review of Diabetic Studies: RDS
E S Yolcu, H Zhao, H Shirwan
Allogeneic islet grafts are subject to rejection by both auto- and alloimmune responses when transplanted into diabetic individuals. T cells play a critical role in the initiation and perpetuation of both autoimmunity and allograft rejection. T cells up-regulate Fas and become sensitive to FasL-mediated killing following antigenic stimulation. Therefore, we tested if immunomodulation with an apoptotic form of FasL chimeric with streptavidin (SA-FasL) is effective in preventing the rejection of allogeneic C57BL/6 islet grafts in chemically diabetic NOD mice...
June 2013: Transplantation Proceedings
Volkert A L Huurman, Cornelis R van der Torren, Pieter Gillard, Robert Hilbrands, Ellen P M W van der Meer-Prins, Gaby Duinkerken, Frans K Gorus, Frans H J Claas, Bart Keymeulen, Dave L Roelen, Daniel G Pipeleers, Bart O Roep
Transplantation of isolated islet of Langerhans cells has great potential as a cure for type 1 diabetes but continuous immune suppressive therapy often causes considerable side effects. Tapering of immunosuppression in successfully transplanted patients would lower patients' health risk. To identify immune biomarkers that may prove informative in monitoring tapering, we studied the effect of tapering on islet auto- and alloimmune reactivity in a pilot study in five transplant recipients in vitro. Cytokine responses to the graft were measured using Luminex technology...
April 25, 2012: Clinical and Experimental Immunology
Huansheng Dong, Tarek M Fahmy, Su M Metcalfe, Steve L Morton, Xiao Dong, Luca Inverardi, David B Adams, Wenda Gao, Hongjun Wang
Two major hurdles need to be surmounted for cell therapy for diabetes: (i) allo-immune rejection of grafted pancreatic islets, or stem/precursor cell-derived insulin-secreting cells; and (ii) continuing auto-immunity against the diabetogenic endogenous target antigen. Nanotherapeutics offer a novel approach to overcome these problems and here we ask if creation of "stealth" islets encapsulated within a thin cage of pegylated material of 100-200 nanometers thick provides a viable option for islet transplantation...
2012: PloS One
V A L Huurman, C R van der Torren, P Gillard, R Hilbrands, E P M W van der Meer-Prins, G Duinkerken, F K Gorus, F H J Claas, B Keymeulen, D L Roelen, D G Pipeleers, B O Roep
Transplantation of isolated islet of Langerhans cells has great potential as a cure for type 1 diabetes but continuous immune suppressive therapy often causes considerable side effects. Tapering of immunosuppression in successfully transplanted patients would lower patients' health risk. To identify immune biomarkers that may prove informative in monitoring tapering, we studied the effect of tapering on islet auto- and alloimmune reactivity in a pilot study in five transplant recipients in vitro. Cytokine responses to the graft were measured using Luminex technology...
August 2012: Clinical and Experimental Immunology
M'Balu A Webb, Ashley R Dennison, Roger F James
Since the advent of islet transplantation, there has been a significant emphasis on the importance of islet purity despite an inevitable associated loss of islet mass during the purification process. One of the key elements of the 'Edmonton Protocol' for islet transplantation published in 2000 was an emphasis on the need for sequential transplants of highly purified islets (averaging 24% beta cell purity) and the close correlation between the numbers of islets transplanted and the success of the procedure. However, the emphasis on islet purity may warrant further consideration as auto transplantation of non-purified islets currently provides the most successful insulin independence rates within the field of islet transplantation...
2012: Biotechnology & Genetic Engineering Reviews
Miao Wang, Jeremy J Racine, Xiaoping Song, Xiaofan Li, Indu Nair, Hongjun Liu, Alina Avakian-Mansoorian, Heather F Johnston, Can Liu, Christine Shen, Mark Atkinson, Ivan Todorov, Fouad Kandeel, Stephen Forman, Brian Wilson, Defu Zeng
Type 1 diabetes (T1D) results from an autoimmune destruction of insulin-producing β cells. Currently, islet transplantation is the only curative therapy for late-stage T1D, but the beneficial effect is limited in its duration, even under chronic immunosuppression, because of the chronic graft rejection mediated by both auto- and alloimmunity. Clinical islet transplantation is also restricted by a severe shortage of donor islets. Induction of mixed chimerism reverses autoimmunity, eliminates insulitis, and reverses new-onset but not late-stage disease in the nonobese diabetic (NOD) mouse model of T1D...
May 9, 2012: Science Translational Medicine
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