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Pancreatic islet transplantation

Michael R Rickels, R Paul Robertson
Pancreatic islet transplantation has become an established approach to β-cell replacement therapy for the treatment of insulin deficient diabetes. Recent progress in techniques for islet isolation, islet culture, and peri-transplant management of the islet transplant recipient have resulted in substantial improvements in metabolic and safety outcomes for patients. For patients requiring total or sub-total pancreatectomy for benign disease of the pancreas, isolation of islets from the diseased pancreas with intrahepatic transplantation of autologous islets can prevent or ameliorate post-surgical diabetes, and for patients previously experiencing painful recurrent acute or chronic pancreatitis, quality-of-life is substantially improved...
December 12, 2018: Endocrine Reviews
Paul C Guest
This chapter describes the propagation and characterization of transplantable insulinoma cells as model of insulin-producing pancreatic islet cells in the rat. Here, the cells are propagated by transplantation into rats followed by harvesting after growth for approximately 1 month. The cells are then purified by Percoll density gradient centrifugation and characterized by pulse-chase radiolabelling and immunoprecipitation of the insulin-related peptides. The results show that the transplantable insulinoma cells produce insulin in a manner similar to that found in normal pancreatic islets...
2019: Methods in Molecular Biology
Jong Hyun Kim, Bo Gi Park, Suel-Kee Kim, Dong-Hyun Lee, Gyung Gyu Lee, Deok-Ho Kim, Byung-Ok Choi, Kyu Back Lee, Jong-Hoon Kim
Bioengineering approaches to regulate stem cell fates aim to recapitulate the in vivo microenvironment. In recent years, manipulating the micro- and nano-scale topography of the stem cell niche has gained considerable interest for the purposes of controlling extrinsic mechanical cues to regulate stem cell fate and behavior in vitro. Here, we established an optimal nanotopographical system to improve 3-dimensional (3D) differentiation of pancreatic cells from human pluripotent stem cells (hPSCs) by testing gradient-pattern chips of nano-scale polystyrene surface structures with varying sizes and shapes...
December 6, 2018: Acta Biomaterialia
Mahban Rahimifard, Shermineh Moini-Nodeh, Kamal Niaz, Maryam Baeeri, Hossein Jamalifar, Mohammad Abdollahi
Objectives: During type-1 diabetes treating by pancreatic islet transplantation, increasing oxidative stress and microbial contaminations are the main reasons of transplantation failure. In this study, we evaluated anti-apoptotic, antioxidant and antimicrobial potentials of phenolic compounds called ellagic acid (EA) and silybin on rat pancreatic islets. Materials and Methods: By doing MTT assay, effective concentrations of EA and silybin were determined as 1500 and 2100 μM, respectively...
September 2018: Iranian Journal of Basic Medical Sciences
Hirotake Komatsu, Colin A Cook, Nelson Gonzalez, Leonard Medrano, Mayra Salgado, Feng Sui, Junfeng Li, Fouad Kandeel, Yoko Mullen, Yu-Chong Tai
Cell transplantation is a promising treatment for complementing lost function by replacing new cells with a desired function, e.g., pancreatic islet transplantation for diabetics. To prevent cell obliteration, oxygen supply is critical after transplantation, especially until the graft is sufficiently re-vascularized. To supply oxygen during this period, we developed a chemical-/electrical-free implantable oxygen transporter that delivers oxygen to the hypoxic graft site from ambient air by diffusion potential...
November 22, 2018: Biofabrication
Hui Wang, Huimin Fan, Jialing Tao, Qixiang Shao, Qing Ding
It has been reported that microRNA-21 (miR-21) augments Th17 responses and contributes to the pathogenesis of autoimmune diseases. Gene knockout or siRNA-induced knockdown of miR-21 in mice resulted in impaired Th17 differentiation and strong resistance to experimental autoimmune encephalomyelitis (EAE). Recently, we validated the miR-21 target IL-10 mRNA and showed that it exerts a pro-inflammatory role by inhibiting IL-10-expressing regulatory B cell (B10) differentiation. The administration of miR-21 antisense oligonucleotides (antagomiR-21) in vivo potently suppressed the severity of EAE, and the suppressive activity was mediated by an increased number of B10 cells...
November 28, 2018: International Immunopharmacology
Mahmoud Hashemitabar, Elham Heidari
Pancreatic β-cells are destroyed by the immune system, in type 1 diabetes (T1D) and are impaired by glucose insensitivity in type 2 diabetes (T2D). Islet-cells transplantation is a promising therapeutic approach based on in vitro differentiation of pluripotent stem cells (PSCs) to insulin-producing cells (IPCs). According to evolutionary stages in β-cell development, there are several distinct checkpoints; each one has a unique characteristic, including definitive endoderm (DE), primitive gut (PG), posterior foregut (PF), pancreatic epithelium (PE), endocrine precursor (EP), and immature β-cells up to functional β-cells...
November 27, 2018: Journal of Cellular Physiology
Tao Wang, Duanqing Pei
Insulin-secreting β cell loss or dysfunction is a feature of both type 1 and type 2 diabetes. Strategies to restore β cell mass are limited, as sources of healthy islets are scarce and mature β cells are not readily expanded in vitro. In this issue of the JCI, Ou et al. report that mature β cell expansion can be induced in situ through epigenetic editing of regulatory elements in pancreatic tissue. Specifically, hypomethylation at imprinting control region 2 (ICR2) in human islets promoted β cell expansion...
November 26, 2018: Journal of Clinical Investigation
Julius Weiss, Andreas Elmer, Markus Béchir, Christian Brunner, Philippe Eckert, Susann Endermann, Renato Lenherr, Mathias Nebiker, Kai Tisljar, Christoph Haberthür, Franz F Immer
BACKGROUND: Various actions have been taken during the last decade to increase the number of organs from deceased donors available for transplantation in Switzerland. This study provides an overview on key figures of the Swiss deceased organ donation and transplant activity between 2008 and 2017. In addition, it puts the evolution of the Swiss donation program's efficiency in relation to the situation in the neighboring countries. METHODS: This study is an analysis of prospective registry data, covering the period from 1 January 2008 to 31 December 2017...
November 20, 2018: BMC Health Services Research
Andrew R Pepper, Antonio Bruni, Rena Pawlick, Doug O'Gorman, Tatsuya Kin, Aducio Thiesen, A M James Shapiro
The paucity of human donors confines the broadened application of β-cell replacement therapy. Insulin-producing cells derived from human embryonic stem cells (hESC), have been recently investigated clinically as a feasible surrogate to primary tissue. Herein, we examine the long-term efficacy of hESC derived pancreatic endoderm cells (PEC) to maintain normoglycemia post-transplant and characterize graft's phenotype.Chemically induced diabetic mice were transplanted with PEC into the subcutaneous device-less site...
November 19, 2018: Diabetes
Diane C Saunders, Marcela Brissova, Neil Phillips, Shristi Shrestha, John T Walker, Radhika Aramandla, Greg Poffenberger, David K Flaherty, Kevin P Weller, Julie Pelletier, Tracy Cooper, Matt T Goff, John Virostko, Alena Shostak, E Danielle Dean, Dale L Greiner, Leonard D Shultz, Nripesh Prasad, Shawn E Levy, Robert H Carnahan, Chunhua Dai, Jean Sévigny, Alvin C Powers
Identification of cell-surface markers specific to human pancreatic β cells would allow in vivo analysis and imaging. Here we introduce a biomarker, ectonucleoside triphosphate diphosphohydrolase-3 (NTPDase3), that is expressed on the cell surface of essentially all adult human β cells, including those from individuals with type 1 or type 2 diabetes. NTPDase3 is expressed dynamically during postnatal human pancreas development, appearing first in acinar cells at birth, but several months later its expression declines in acinar cells while concurrently emerging in islet β cells...
November 12, 2018: Cell Metabolism
S S Kim, H J Jang, M Y Oh, J H Lee, K S Kang
BACKGROUND: The transplantation of isolated pancreatic islets is a promising treatment for diabetes. Curcumin has been used for its pharmacologic effects, such as antidiabetic and anti-inflammatory activities. Tetrahydrocurcumin (THC), one of the major metabolites of curcumin, has been reported to have antioxidant and anti-inflammatory activities. This study examines the hypothesis that preoperative THC treatment can attenuate ischemic damage and apoptosis before islet transplantation...
November 2018: Transplantation Proceedings
Christine A Beamish, A Osama Gaber, Solmaz F Afshar, Daniel W Fraga, Dale J Hamilton, Omaima M Sabek
Beta-cell dedifferentiation as shown by cellular colocalization of insulin with glucagon and/or vimentin, and decreased expression of MAFA and/or urocortin3 has been suggested to contribute to metabolic decompensation in type 2 diabetes, and was recently described postimplantation in islet allotransplant patients. Dysglycaemia and diabetes mellitus are often encountered preoperatively in patients undergoing pancreatectomy and islet autotransplantation (PIAT). In this series of case reports, we document variation in islet phenotypic identity in three patients with chronic pancreatitis (CP) without diabetes or significant insulin resistance who subsequently underwent PIAT...
October 29, 2018: American Journal of Transplantation
P A Senior, J H Pettus
Many people with Type 1 diabetes struggle with the burden of self-management and are unable to achieve optimal glycaemic control without risk of hypoglycaemia. Future therapies with the potential to reduce the risk for short- and long-term complications while simultaneously reducing the burden of diabetes are therefore attractive. β-cell replacement is one strategy which might achieve this. Islet transplantation is limited by organ supply and the risks of long-term immunosuppression. Encapsulated stem-cell-derived β cells have the potential to address both of these issues and phase I/II clinical trials of encapsulated pancreatic progenitors have begun...
October 25, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
Gung Lee, Hagoon Jang, Ye Young Kim, Sung Sik Choe, Jinuk Kong, Injae Hwang, Jeu Park, Seung-Soon Im, Jae Bum Kim
Sterol responsive element-binding protein 1c (SREBP1c) is a key transcription factor for de novo lipogenesis. Although SREBP1c is expressed in pancreatic islets, its physiological roles in pancreatic β cells are largely unknown. In this study, we demonstrate that SREBP1c regulates β cell compensation under metabolic stress. SREBP1c expression level was augmented in pancreatic islets from obese and diabetic animals. In pancreatic β cells, SREBP1c activation promoted the expression of cell cycle genes and stimulated β cell proliferation through its novel target gene, PAX4 Compared to SREBP1c +/+ mice, SREBP1c -/- mice showed glucose intolerance with low insulin levels...
October 23, 2018: Diabetes
Leo P Graves, Mine Aksular, Riyadh A Alakeely, Daniel Ruiz Buck, Adam C Chambers, Fernanda Murguia-Meca, Juan-Jose Plata-Muñoz, Stephen Hughes, Paul R V Johnson, Robert D Possee, Linda A King
Pancreatic islet transplantation is a promising treatment for type 1 diabetes mellitus offering improved glycaemic control by restoring insulin production. Improved human pancreatic islet isolation has led to higher islet transplantation success. However, as many as 50% of islets are lost after transplantation due to immune responses and cellular injury, gene therapy presents a novel strategy to protect pancreatic islets for improved survival post-transplantation. To date, most of the vectors used in clinical trials and gene therapy studies have been derived from mammalian viruses such as adeno-associated or retrovirus...
October 20, 2018: Viruses
Tadas Kasputis, Daniel Clough, Fallon Noto, Kevin Rychel, Briana Dye, Lonnie D Shea
Type I diabetes mellitus, which affects an estimated 1.5 million Americans, is caused by autoimmune destruction of the pancreatic beta cells that results in the need for life-long insulin therapy. Allogeneic islet transplantation for the treatment of type I diabetes is a therapy in which donor islets are infused intrahepatically, which has led to the transient reversal of diabetes. However, therapeutic limitations of allogeneic transplantation, which include a shortage of donor islets, long-term immunosuppression, and high risk of tissue rejection, have led to the investigation of embryonic or induced pluripotent stem cells as an unlimited source of functional beta-cells...
May 14, 2018: ACS Biomaterials Science & Engineering
Xinyu Li, Qiang Meng, Lei Zhang
Pancreatic islet transplantation as a therapeutic option for type 1 diabetes mellitus is gaining widespread attention because this approach can restore physiological insulin secretion, minimize the risk of hypoglycemic unawareness, and reduce the risk of death due to severe hypoglycemia. However, there are many obstacles contributing to the early mass loss of the islets and progressive islet loss in the late stages of clinical islet transplantation, including hypoxia injury, instant blood-mediated inflammatory reactions, inflammatory cytokines, immune rejection, metabolic exhaustion, and immunosuppression-related toxicity that is detrimental to the islet allograft...
2018: Journal of Immunology Research
Xiao Wei, Dan Zhu, Chenchen Feng, Guofang Chen, Xiaodong Mao, Qifeng Wang, Jie Wang, Chao Liu
Cyclosporin A (CsA) is widely used as an immunosuppressor in the context of organ transplantation or autoimmune disorders. Recent studies have revealed the detrimental effects of CsA on insulin resistance and pancreatic β cell failure; however, the molecular mechanisms are unknown. The present study sought to confirm the associations between CsA and β cell failure, and to investigate the roles of proinsulin folding and endoplasmic reticulum (ER) stress in CsA-induced β cell failure. The viability of MIN6 cells treated with CsA was evaluated with MTT assay...
November 2018: Experimental and Therapeutic Medicine
Sharath Belame Shivakumar, Dinesh Bharti, Raghavendra Baregundi Subbarao, Ju-Mi Park, Young-Bum Son, Imran Ullah, Yong-Ho Choe, Hyeong-Jeong Lee, Bong-Wook Park, Sung-Lim Lee, Gyu-Jin Rho
Following success of pancreatic islet transplantation in the treatment of Type I diabetes mellitus, there is a growing interest in using cell-based treatment approaches. However, severe shortage of donor islets-pancreas impeded the growth, and made researchers to search for an alternative treatment approaches. In this context, recently, stem cell-based therapy has gained more attention. The current study demonstrated that epigenetic modification improves the in vitro differentiation of Wharton's jelly mesenchymal stem cells (WJMSCs) into pancreatic endocrine-like cells...
October 21, 2018: Journal of Cellular Physiology
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