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Islet transplantation

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
Kevin Vivot, Malika A Benahmed, Elodie Seyfritz, William Bietiger, Karim Elbayed, Elisa Ruhland, Allan Langlois, Elisa Maillard, Michel Pinget, Nathalie Jeandidier, Jean-Pierre Gies, Izzie-Jacques Namer, Séverine Sigrist, Nathalie Reix
Intrahepatic transplantation of islets requires a lot of islets because more than 50% of the graft is lost during the 24 hours following transplantation. We analyzed, in a rat model, early post-transplantation inflammation using systemic inflammatory markers, or directly in islet-transplanted livers by immunohistochemistry. (1)H HRMAS NMR was employed to investigate metabolic responses associated with the transplantation. Inflammatory markers (Interleukin-6, α2-macroglobulin) are not suitable to follow islet reactions as they are not islet specific...
2016: International Journal of Biological Sciences
Ingrid K Hals, Rinku Singh, Zuheng Ma, Hanne Scholz, Anneli Björklund, Valdemar Grill
We tested whether exposure of beta cells at reduced glucose leads to mitochondrial adaptions and whether such adaptions modulate effects of hypoxia. Rat islets, human islets and INS-1 832/13 cells were pre-cultured short term at half standard glucose concentrations (5.5 mM for rat islets and cells, 2.75 mM for human islets) without overtly negative effects on subsequently measured function (insulin secretion and cellular insulin contents) or on viability. Culture at half standard glucose upregulated complex I and tended to upregulate complex II in islets and INS-1 cells alike...
October 20, 2016: Islets
Rauf Shahbazov, Gumpei Yoshimatsu, Waqas Z Haque, Omar S Khan, Giovanna Saracino, Michael C Lawrence, Peter T Kim, Nicholas Onaca, Bashoo Naziruddin, Marlon F Levy
BACKGROUND: The impact of pylorus preserving procedures (PP) on total pancreatectomy with islet autotransplantation (TPIAT) has not been examined. This study aimed to investigate the clinical impact of the PP on TPIAT. METHODS: The Baylor Simmons Transplant Institute database was queried to identify seventy-three patients who underwent TPIAT from 2006 to 2014. All patients were investigated in postoperative complications, long-term nutritional status, and graft function...
October 8, 2016: American Journal of Surgery
Jie Qin, Yusuke Arakawa, Miwa Morita, John J Fung, Shiguang Qian, Lina Lu
BACKGROUND: Islet transplantation is a promising therapeutic approach for restore the physical response to blood glucose in type 1 diabetes. Current chronic use of immunosuppressive reagents for preventing islet allograft rejection is associated with severe complications. In addition, many of the immunosuppressive drugs are diabetogenic. The induction of transplant tolerance to eliminate the dependency on immunosuppression is ideal, but remains challenging. METHODS: Addition of hepatic stellate cells allowed generation of myeloid-derived suppressor cells (MDSC) from precursors in mouse bone marrow...
October 17, 2016: Transplantation
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
Kevin V Chow, Emma M Carrington, Yifan Zhan, Andrew M Lew, Robyn M Sutherland
Islet transplantation can cure type 1 diabetes, but is limited by lack of donor organs and early graft dysfunction, such that many patients require multiple transplants to achieve insulin independence. Monocyte derived dendritic cells (moDCs) arise during inflammation and allograft encounters where they can promote various innate and adaptive immune responses. To determine whether moDCs impair early graft function following allogeneic islet transplantation, we transplanted MHC-mismatched BALB/c (H-2d) islets into diabetic C57BL/6-CCR2...
October 13, 2016: Cell Transplantation
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
Masayuki Shimoda, Shinichi Matsumoto
Allogeneic islet transplantation has become a viable treatment for patients with unstable type 1 diabetes; however, donor shortage and the necessity for immunosuppressive drugs are the major drawbacks of this approach. Microencapsulated porcine islet xenotransplantation could solve these drawbacks. Clinical porcine islet xenotransplantation as well as microencapsulated islet transplantation has been conducted without significant side effects. However, these transplantations are not as efficacious as allogeneic naked islet transplantation...
2017: Methods in Molecular Biology
Rahul Krishnan, David Ko, Clarence E Foster, Wendy Liu, A M Smink, Bart de Haan, Paul De Vos, Jonathan R T Lakey
Transplantation of alginate-encapsulated islets has the potential to treat patients suffering from type I diabetes, a condition characterized by an autoimmune attack against insulin-secreting beta cells. However, there are multiple immunological challenges associated with this procedure, all of which must be adequately addressed prior to translation from trials in small animal and nonhuman primate models to human clinical trials. Principal threats to graft viability include immune-mediated destruction triggered by immunogenic alginate impurities, unfavorable polymer composition and surface characteristics, and release of membrane-permeable antigens, as well as damage associated molecular patterns (DAMPs) by the encapsulated islets themselves...
2017: Methods in Molecular Biology
Riccardo Calafiore, Giuseppe Basta, Pia Montanucci
Microencapsulation technology, based on use of alginic acid biopolymers, has been devised many years ago. However, when intended for enveloping human islets for transplantation purposes, the method needs to be up-scaled and implemented with care being taken to comply with simple but important measures. It is almost indispensable to rely on an ultrapurified alginic polymers: in fact, any, even minimal, alginate contamination with endotoxins, pyrogens, and proteins could provoke the host's inflammatory reaction upon graft, with heavy adverse consequences on the capsules immunoprotective properties, hence on graft survival per se...
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
John Patrick McQuilling, Sivanandane Sittadjody, Rajesh Pareta, Samuel Pendergraft, Clancy J Clark, Alan C Farney, Emmanuel C Opara
Microencapsulation of islets is a procedure used to immunoisolate islets in order to obviate the need for immunosuppression of islet transplant recipients. Although microencapsulated islets have routinely been transplanted in the peritoneal cavity, the ideal site for their engraftment remains to be determined. The omentum, a highly vascularized tissue, has been proposed as an alternative site for microencapsulated islet transplantation. An added benefit to the omentum is that implanted microcapsules can be easily retrieved for post-transplant evaluation...
2017: Methods in Molecular Biology
Marcus D Darabbie, Emmanuel C Opara
The promise of pancreatic islet transplantation is hindered by organ shortage, and the need for immunosuppression of transplant recipient in order to prevent rejection. Alginate microencapsulation can overcome these hurdles; however further optimization of this technique is required. Among the critical factors to be optimized is the durability of alginate microcapsules, which can be determined by their mechanical strength tests. Here we describe several simple and reliable methods to assist in assessing the mechanical strength of alginate beads...
2017: Methods in Molecular Biology
William F Kendall, Emmanuel C Opara
Application of microencapsulation to the immunoisolation of pancreatic islets holds promise for expanding the use of islet transplantation as a treatment option for Type 1 diabetes. It is generally believed that successful development of a reliable methodology will ideally allow for transplantation of pancreatic islets that are protected from the immune system, thereby obviating the need for the use of immunosuppressive drugs and their attendant side effects. In addition, this technology has the potential to expand the donor pool as islets from nonhuman donors could be used as xenografts in human patients...
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
Youngjin Kim, Hyeongseok Kim, Ung Hyun Ko, Youjin Oh, Ajin Lim, Jong-Woo Sohn, Jennifer H Shin, Hail Kim, Yong-Mahn Han
Insulin secretion is elaborately modulated in pancreatic ß cells within islets of three-dimensional (3D) structures. Using human pluripotent stem cells (hPSCs) to develop islet-like structures with insulin-producing ß cells for the treatment of diabetes is challenging. Here, we report that pancreatic islet-like clusters derived from hESCs are functionally capable of glucose-responsive insulin secretion as well as therapeutic effects. Pancreatic hormone-expressing endocrine cells (ECs) were differentiated from hESCs using a step-wise protocol...
October 12, 2016: Scientific Reports
Shuyun Liu, Lanlan Zhang, Jingqiu Cheng, Yanrong Lu, Jingping Liu
Inflammatory response is a major cause of grafts dysfunction in islet transplantation. Hepatocyte growth factor (HGF) had shown anti-inflammatory activity in multiple diseases. In this study, we aim to deliver HGF by self-assembling peptide/heparin (SAP/Hep) hybrid gel to protect β-cell from inflammatory injury. The morphological and slow release properties of SAPs were analyzed. Rat INS-1 β-cell line was treated with tumor necrosis factor α in vitro and transplanted into rat kidney capsule in vivo, and the viability, apoptosis, function, and inflammation of β-cells were evaluated...
2016: International Journal of Nanomedicine
Ka Hei Chan, Rahul Krishnan, Michael Alexander, Jonathan Rt Lakey
The islets of Langerhans are endocrine tissue clusters that secrete hormones that regulate the body's glucose, carbohydrate and fat metabolism, the most important of which is insulin, a hormone secreted by β cells within the islets. In certain instances, a person's own immune system attacks and destroys them leading to the development of Type 1 diabetes (T1D), a lifelong condition that needs daily insulin administration to maintain health and prolong survival. Islet transplantation is a surgical procedure that has demonstrated the ability to normalize blood sugar levels for up to a few years, but the need for chronic immunosuppression relegates it to a last resort that is often only used sparingly, and in seriously-ill patients...
October 10, 2016: Cell Transplantation
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