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pancreas transplantation islets

Kathrin Fielitz, Kristina Althoff, Katleen De Preter, Julie Nonnekens, Jasmin Ohli, Sandra Elges, Wolfgang Hartmann, Günter Klöppel, Thomas Knösel, Marc Schulte, Ludger Klein-Hitpass, Daniela Beisser, Henning Reis, Annette Eyking, Elke Cario, Johannes H Schulte, Alexander Schramm, Ulrich Schüller
Amplification or overexpression of MYCN is involved in development and maintenance of multiple malignancies. A subset of these tumors originates from neural precursors, including the most aggressive forms of the childhood tumors, neuroblastoma and medulloblastoma. In order to model the spectrum of MYCN-driven neoplasms in mice, we transgenically overexpressed MYCN under the control of the human GFAP-promoter that, among other targets, drives expression in neural progenitor cells. However, LSL-MYCN;hGFAP-Cre double transgenic mice did neither develop neural crest tumors nor tumors of the central nervous system, but presented with neuroendocrine tumors of the pancreas and, less frequently, the pituitary gland...
October 19, 2016: Oncotarget
Jamal Mohammadi Ayenehdeh, Bahareh Niknam, Seyed Mahmoud Hashemi, Hossein Rahavi, Nima Rezaei, Masoud Soleimani, Nader Tajik
BACKGROUND: Islet transplantation could be an ideal alternative treatment to insulin therapy for type 1 diabetes Mellitus (T1DM). This clinical and experimental field requires a model that covers problems such as requiring a large number of functional and viable islets, the optimal transplantation site, and the prevention of islet dispersion. Hence, the methods of choice for isolation of functional islets and transplantation are crucial. METHODS: The present study has introduced an experimental model that overcomes some critical issues in islet transplantation, including in situ pancreas perfusion by digestive enzymes through common bile duct...
October 18, 2016: Iranian Biomedical Journal
Masayuki Shimoda, Shinichi Matsumoto
Allogeneic islet transplantation has become a viable option for the treatment of unstable type 1 diabetes; however, donor shortage and the necessity for immunosuppressive drugs are two major drawbacks of this treatment. Microencapsulated porcine islets can solve both of these drawbacks, and clinical trials have been conducted. Previous clinical trials demonstrated the safety and marginal efficacy of this treatment; therefore, it is necessary to improve its efficacy. The production of microencapsulated porcine islets consists of pancreas procurement, islet isolation, and microencapsulation...
2017: Methods in Molecular Biology
Kevin Enck, John Patrick McQuilling, Giuseppe Orlando, Riccardo Tamburrini, Sittadjody Sivanandane, Emmanuel C Opara
Islet transplantation (IT) has recently been shown to be a promising alternative to pancreas transplantation for reversing diabetes. IT requires the isolation of the islets from the pancreas, and these islets can be used to fabricate a bio-artificial pancreas. Enzymatic digestion is the current gold standard procedure for islet isolation but has lingering concerns. One such concern is that it has been shown to damage the islets due to nonselective tissue digestion. This chapter provides a detailed description of a nonenzymatic method that we are exploring in our lab as an alternative to current enzymatic digestion procedures for islet isolation from human and nonhuman pancreatic tissues...
2017: Methods in Molecular Biology
William F Kendall, Emmanuel C Opara
Since the discovery of insulin by Banting and Best in 1921, the prognosis and treatment options for individuals with diabetes have improved. The development of various insulin types, various oral agents, and insulin pumps have improved the available medical options for individuals afflicted with diabetes. The current need for frequent blood glucose monitoring imposed by multiple daily insulin injections, result in significant life-style challenges for in individuals afflicted with Type 1 diabetes (T1D). In contrast the use of surgical interventions, such as whole organ pancreas transplantation (PT) requires less-intensive glucose monitoring while the organ is viable...
2017: Methods in Molecular Biology
Varna Sharma, Michael Hunckler, Melur K Ramasubramanian, Emmanuel C Opara, Kalyan C Katuri
Bioartificial pancreas made of insulin-secreting islets cells holds great promise in the treatment of individuals with Type-1 diabetes. Successful islet cell microencapsulation in biopolymers is a key step for providing immunoisolation of transplanted islet cells. Because of the variability in the size and shape of pancreatic islets, one of the main obstacles in their microencapsulation is the inability to consistently control shape, size, and microstructure of the encapsulating biopolymer capsule. In this chapter, we provide a detailed description of a microfluidic approach to islet cell encapsulation in alginate that might address the microencapsulation challenges...
2017: Methods in Molecular Biology
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
Hong-Tu Li, Fang-Xu Jiang, Ping Shi, Tao Zhang, Xiao-Yu Liu, Xue-Wen Lin, Zhong-Yan San, Xi-Ning Pang
Islet transplantation provides curative treatments to patients with type 1 diabetes, but donor shortage restricts the broad use of this therapy. Thus, generation of alternative transplantable cell sources is intensively investigated worldwide. We previously showed that bone marrow-derived mesenchymal stem cells (bmMSCs) can be reprogrammed to pancreatic-like cells through simultaneously forced suppression of Rest/Nrsf (repressor element-1 silencing transcription factor/neuronal restrictive silencing factor) and Shh (sonic hedgehog) and activation of Pdx1 (pancreas and duodenal transcription factor 1)...
October 3, 2016: In Vitro Cellular & Developmental Biology. Animal
Nancy El-Hossary, Hamdy Hassanein, Abdel Wahab El-Ghareeb, Hisham Issa
AIM: To evaluate the efficiency of mesenchymal stem cells isolated from Wharton's jelly (WJ-MSCs) through either the intravenous or intraperitoneal transplantations into streptozotocin (STZ)-induced diabetic rats as a therapy for type 1 diabetes mellitus (T1DM). METHODOLOGY: A rat model with STZ induction was established and the rats were divided into 3 groups: a tail vein injection group, an intraperitoneal injection group and a STZ control group. Following transplantation, blood glucose levels were monitored weekly then the pancreatic tissues were collected to examine the pancreatic islets by histopathology and morphometric studies...
September 21, 2016: Diabetes Research and Clinical Practice
Jong-Min Kim, Jun-Seop Shin, Byoung-Hoon Min, Hyun-Je Kim, Jung-Sik Kim, Il-Hee Yoon, Won-Young Jeong, Ga-Eul Lee, Min-Sun Kim, Ju-Eun Kim, Sang-Man Jin, Chung-Gyu Park
BACKGROUND: Diabetes mellitus (DM) model using streptozotocin (STZ) which induces chemical ablation of β cell in the pancreas has been widely used for various research purposes in non-human primates. However, STZ has been known to have a variety of adverse effects such as nephrotoxicity, hepatotoxicity, and even mortality. The purpose of this study is to report DM induction by STZ, toxicity associated with STZ and procedure and complication of exogenous insulin treatment for DM management in rhesus monkeys (Macaca mulatta) that are expected to be transplanted with porcine islets within 2 months...
September 27, 2016: Xenotransplantation
Issei Saitoh, Masahiro Sato, Miki Soda, Emi Inada, Yoko Iwase, Tomoya Murakami, Hayato Ohshima, Haruaki Hayasaki, Hirofumi Noguchi
Type 1 diabetes occurs due to the autoimmune destruction of pancreatic β-cells in islets. Transplantation of islets is a promising option for the treatment of patients with type 1 diabetes that experience hypoglycemic unawareness despite maximal care, but the present shortage of donor islets hampers such transplantation. Transplantation of insulin-producing cells derived from the patients themselves would be one of the most promising approaches to cure type 1 diabetes. Previously, we demonstrated that insulin-producing cells could be produced by transfecting murine pancreatic cells with Yamanaka's reprogramming factors...
2016: PloS One
Keiko Omori, Eiji Kobayashi, Jeffrey Rawson, Masafumi Takahashi, Yoko Mullen
Prolonged pancreas cold ischemia is known to negatively correlate with islet isolation outcomes, hindering successful islet transplantation to treat Type-1 Diabetes. Due to poor islet isolation outcome, pancreata with over 16 h cold ischemia are currently not considered for islet transplantation. Mechanisms involved in pancreas cold ischemia/rewarming mediated islet damage during islet isolation and culture are not well understood. Using an en bloc cold preserved rat pancreas preparation, we attempted to clarify possible mechanisms of islet death associated with prolonged pancreas cold ischemia and subsequent rewarming...
October 2016: Cryobiology
Wayne J Hawthorne, Lindy Williams, Yi Vee Chew
The overarching success of islet transplantation relies on the success in the laboratory to isolate the islets. This chapter focuses on the processes of human islet cell isolation and the ways to optimally provide islet cells for transplantation. The major improvements in regards to the choice of enzyme type, way the digested pancreas tissue is handled to best separate islets from the acinar and surrounding tissues, the various methods of purification of the islets, their subsequent culture and quality assurance to improve outcomes to culminate in safe and effective islet transplantation will be discussed...
2016: Advances in Experimental Medicine and Biology
Wayne J Hawthorne
For more than two decades we have been refining advances in islet cell transplantation as a clinical therapy for patients suffering from type 1 diabetes. A great deal of effort has gone to making this a viable therapy for a broader range of patients with type 1 diabetes. Clinical results have progressively improved, demonstrating clinical outcomes on par with other organ transplants, specifically in terms of insulin independence, graft and patient survival. We are now at the point where islet cell transplantation, in the form of allotransplantation, has become accepted as a clinical therapy in adult patients affected by type 1 diabetes, in particular those suffering from severe hypoglycaemic unawareness...
2016: Advances in Experimental Medicine and Biology
Miriam Ramírez-Domínguez
Until the discovery of insulin in the twentieth century, diabetes mellitus was a mortal disease with an unclear origin and physiology. Despite the appearance of the concept in an Egyptian papyrus dated c.1550 BC, and the documentation of its study by ancient Chinese, the term "diabetes" was only coined by the Greek Aretaeus in the second century AD. In Europe, the study of diabetes was largely ignored until the seventeenth century, when the characteristic sweet flavor of diabetic urine was first described. However, the link between diabetes and the pancreas was not discovered until 1889 by Minkowski and von Mering, long after the first description of the pancreatic islets by Paul Langerhans in 1869...
2016: Advances in Experimental Medicine and Biology
M Karakose, F A Pinarli, M S Arslan, G Boyuk, B Boztok, A Albayrak, A T Ulus, E Cakal, T Delibasi
BACKGROUND: Currently, the most commonly used site for clinical islet transplantation is the liver although it is far from being an ideal site. Low oxygen tension and the induction of an inflammatory response impair islet implantation and lead to significant early loss of islet. The present study aimed to investigate and compare the efficacy of islet transplantation to the ovary and kidney subcapsule in diabetic rats. METHODS: The study was performed with 3 groups of rats (control, ovary, and kidney subcapsule) including 6 Sprague female rats each...
July 2016: Transplantation Proceedings
Elisa Corritore, Yong-Syu Lee, Etienne M Sokal, Philippe A Lysy
Thorough research on the capacity of human islet transplantation to cure type 1 diabetes led to the achievement of 3- to 5-year-long insulin independence in nearly half of transplanted patients. Yet, translation of this technique to clinical routine is limited by organ shortage and the need for long-term immunosuppression, restricting its use to adults with unstable disease. The production of new bona fide β cells in vitro was thus investigated and finally achieved with human pluripotent stem cells (PSCs)...
August 2016: Therapeutic Advances in Endocrinology and Metabolism
Jordi Rovira, María Jose Ramírez-Bajo, Elisenda Banon-Maneus, Daniel Moya-Rull, Pedro Ventura-Aguiar, Natalia Hierro-Garcia, Marta Lazo-Rodriguez, Ignacio Revuelta, Armando Torres, Federico Oppenheimer, Josep M Campistol, Fritz Diekmann
BACKGROUND: Sirolimus (SRL) has been associated with new-onset diabetes mellitus after transplantation. The aim was to determine the effect of SRL on development of insulin resistance and β -cell toxicity. METHODS: Lean Zucker rat (LZR) and obese Zucker rat (OZR) were distributed into groups: vehicle and SRL (0.25, 0.5, or 1.0 mg/kg) during 12 or 28 days. Intraperitoneal glucose tolerance test (IPGTT) was evaluated at days 0, 12, 28, and 45. Islet morphometry, β-cell proliferation, and apoptosis were analyzed at 12 days...
February 2016: Transplantation Direct
Zhu-Zeng Yin, Shu-Sen Wang, Qiang Li, Ying Huang, Li Chen, Gang Chen, Rong Liu, Xi-Mo Wang
Intraportal transplantation of islets is no longer considered to be an ideal procedure and finding the extrahepatic alternative site is becoming a subject of high priority. Herein, in this study, we would introduce our initial outcomes of using gastric submucosa (GS) and liver as sites of islet autotransplantation in pancreatectomized diabetic Beagles. Total pancreatectomy was performed in Beagles and then their own islets extracted from the excised pancreas were transplanted into GS (GS group, n=8) or intrahepatic via portal vein (PV group, n=5)...
August 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Aruna V Vanikar, Hargovind L Trivedi, Umang G Thakkar
Type 1 diabetes mellitus (T1DM) is an autoimmune disease causing progressive destruction of pancreatic β cells, ultimately resulting in loss of insulin secretion producing hyperglycemia usually affecting children. Replacement of damaged β cells by cell therapy can treat it. Currently available strategies are insulin replacement and islet/pancreas transplantation. Unfortunately these offer rescue for variable duration due to development of autoantibodies. For pancreas/islet transplantation a deceased donor is required and various shortfalls of treatment include quantum, cumbersome technique, immune rejection and limited availability of donors...
September 2016: Cytotherapy
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