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Islet transplantation

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https://www.readbyqxmd.com/read/29140547/islet-transplantation-as-safe-and-efficacious-method-to-restore-glycemic-control-and-to-avoid-severe-hypoglycemia-after-donor-organ-failure-in-pancreas-transplantation
#1
Philipp A Gerber, Michel Hochuli, Bara D Benediktsdottir, Richard A Zuellig, Oliver Tschopp, Michael Glenck, Olivier de Rougemont, Christian Oberkofler, Giatgen A Spinas, Roger Lehmann
The aim of this study was to assess safety and efficacy of islet transplantation after initial pancreas transplantation with subsequent organ failure. Patients undergoing islet transplantation at our institution after pancreas organ failure were compared to a control group of patients with pancreas graft failure, but without islet transplantation and to a group receiving pancreas re-transplantation. 10 patients underwent islet transplantation after initial pancreas transplantation failed and were followed for a median of 51 months...
November 15, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29135052/enhanced-effect-of-human-mesenchymal-stem-cells-expressing-human-tnf-%C3%AE-r-fc-and-ho-1-gene-on-porcine-islet-xenotransplantation-in-humanized-mice
#2
Han-Sin Lee, Sanghyun Song, Du Yeon Shin, Geun-Soo Kim, Jong-Hyun Lee, Chan Woo Cho, Kyo Won Lee, Hyojun Park, Curie Ahn, Jaeseok Yang, Heung-Mo Yang, Jae Berm Park, Sung-Joo Kim
BACKGROUND: Porcine islet xenotransplantation is considered an attractive alternative treatment for type 1 diabetes mellitus. However, it is largely limited because of initial rejection due to Instant Blood-Mediated Inflammatory Reaction (IBMIR), oxidative stress, and inflammatory responses. Recently, soluble tumor necrosis factor-ɑ receptor type I (sTNF-αR) and heme oxygenase (HO)-1 genes (HO-1/sTNF-αR) have been shown to improve the viability and functionality of porcine islets after transplantation...
November 14, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29131417/culturing-with-modified-egm2-medium-enhances-porcine-neonatal-islet-like-cell-clusters-resistance-to-apoptosis-in-islet-xenotransplantation
#3
Xiaoqian Ma, Cejun Yang, Juan Zhang, Jia Wang, Wei Li, Chang Xu, Pengfei Rong, Bin Ye, Minghua Wu, Jianhui Jiang, Shounan Yi, Wei Wang
BACKGROUND: Neonatal pig islet-like cell clusters (NICC) are an attractive source of insulin-producing tissue for potential transplantation treatment of type 1 diabetic patients. However, a considerable loss of NICC after their transplantation due to apoptosis resulted from islet isolation and instant blood-mediated inflammatory reaction remains to be overcome. METHODS: EGM2 medium depleted with hydrocortisone and supplemented with 50 mmol/L isobutylmethylxanthine, 10 mmol/L nicotinamide, and 10 mmol/L glucose was used to culture NICC at day 1, the day after isolation and changed every other day...
November 12, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29131413/the-effect-of-epitope-based-ligation-of-icam-1-on-survival-and-retransplantation-of-pig-islets-in-nonhuman-primates
#4
Jae-Il Lee, Jiyeon Kim, Yun-Jung Choi, Hi-Jung Park, Hye-Jin Park, Hae Joo Wi, Sunok Yoon, Jun-Seop Shin, Jin Kyun Park, Kyeong Cheon Jung, Eun Bong Lee, Hee Jung Kang, Eung Soo Hwang, Sang-Joon Kim, Chung-Gyu Park, Seong Hoe Park
BACKGROUND: Pig islet xenotransplantation is a promising alternative to allogeneic transplantation. However, the wide immunologic barrier between pigs and primates limits the long-term survival of the graft. MD-3, a novel monoclonal antibody (mAb) that recognizes a particular epitope of human ICAM-1, can render T cells tolerant to a xenograft by arresting dendritic cell maturation. We report the long-term survival of adult wild-type pig islets and successful retransplantation in nonhuman primates using a protocol comprising induction with MD-3 mAb and maintenance with anti-CD154 mAb and sirolimus...
November 12, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29128846/tissue-adhesive-fk506-loaded-polymeric-nanoparticles-for-multi-layered-nano-shielding-of-pancreatic-islets-to-enhance-xenograft-survival-in-a-diabetic-mouse-model
#5
Tung Thanh Pham, Tiep Tien Nguyen, Shiva Pathak, Shobha Regmi, Hanh Thuy Nguyen, Tuan Hiep Tran, Chul Soon Yong, Jong Oh Kim, Pil-Hoon Park, Min Hui Park, Young Kyung Bae, Jeong Uk Choi, Youngro Byun, Cheol-Hee Ahn, Simmyung Yook, Jee-Heon Jeong
This study aims to develop a novel surface modification technology to prolong the survival time of pancreatic islets in a xenogenic transplantation model, using 3,4-dihydroxyphenethylamine (DOPA) conjugated poly(lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) nanoparticles (DOPA-NPs) carrying immunosuppressant FK506 (FK506/DOPA-NPs). The functionalized DOPA-NPs formed a versatile coating layer for antigen camouflage without interfering the viability and functionality of islets. The coating layer effectively preserved the morphology and viability of islets in a co-culture condition with xenogenic lymphocytes for 7 days...
November 1, 2017: Biomaterials
https://www.readbyqxmd.com/read/29123178/a-nanobody-based-tracer-targeting-dpp6-for-non-invasive-imaging-of-human-pancreatic-endocrine-cells
#6
Alexander Balhuizen, Sam Massa, Iris Mathijs, Jean-Valery Turatsinze, Jens De Vos, Stéphane Demine, Catarina Xavier, Olatz Villate, Isabelle Millard, Dominique Egrise, Carmen Capito, Raphaël Scharfmann, Pieter In't Veld, Piero Marchetti, Serge Muyldermans, Serge Goldman, Tony Lahoutte, Luc Bouwens, Decio L Eizirik, Nick Devoogdt
There are presently no reliable ways to quantify endocrine cell mass (ECM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. To address this unmet need, we coupled RNA sequencing of human pancreatic islets to a systems biology approach to identify new biomarkers of the endocrine pancreas. Dipeptidyl-Peptidase 6 (DPP6) was identified as a target whose mRNA expression is at least 25-fold higher in human pancreatic islets as compared to surrounding tissues and is not changed by proinflammatory cytokines...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29121094/pleckstrin-homology-like-domain-family-a-member-3-phlda3-deficiency-improves-islets-engraftment-through-the-suppression-of-hypoxic-damage
#7
Naoaki Sakata, Yohko Yamaguchi, Yu Chen, Masayuki Shimoda, Gumpei Yoshimatsu, Michiaki Unno, Shoichiro Sumi, Rieko Ohki
Islet transplantation is a useful cell replacement therapy that can restore the glycometabolic function of severe diabetic patients. It is known that many transplanted islets failed to engraft, and thus, new approaches for overcoming graft loss that may improve the outcome of future clinical islet transplantations are necessary. Pleckstrin homology-like domain family A, member 3 (PHLDA3) is a known suppressor of neuroendocrine tumorigenicity, yet deficiency of this gene increases islet proliferation, prevents islet apoptosis, and improves their insulin-releasing function without causing tumors...
2017: PloS One
https://www.readbyqxmd.com/read/29120883/equipping-the-islet-graft-for-self-defence-targeting-nuclear-factor-%C3%AE%C2%BAb-and-implications-for-tolerance
#8
Nathan W Zammit, Shane T Grey
PURPOSE OF REVIEW: Clinical islet transplantation does not enjoy the success seen for solid organ transplants, indicating a need for new therapeutic approaches to improve patient outcomes. This has prompted investigation into islet autonomous factors and pathways that may represent druggable targets. These have the potential to synergize with approaches aimed at generating graft-specific tolerance. RECENT FINDINGS: There are emerging data that nuclear factor κB (NF-κB) activation can prevent and or overcome tolerance, whereas dampening NF-κB activation in immune cells is associated with prolonged allograft survival...
November 7, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29101297/mesenchymal-stromal-cells-improve-human-islet-function-through-released-products-and-extracellular-matrix
#9
Ahmed A Arzouni, Andreia Vargas-Seymour, Chloe L Rackham, Paramjeet Dhadda, Guo-Cai Huang, Pratik Choudhary, Nance Nardi, Aileen J F King, Peter M Jones
Aims: The aims of the current study were (i) to determine whether the reported beneficial effects of mesenchymal stromal cells (MSCs) on mouse islet function extend to clinically relevant human tissues (islets and MSCs), enabling translation into improved protocols for clinical human islet transplantation; and (ii) to identify possible mechanisms through which human MSCs influence human islet function. Materials and methods: Human islets were co-cultured with human adipose tissue-derived MSCs (hASCs) or pretreated with its products - extracellular matrix (ECM) and annexin A1 (ANXA1)...
November 3, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29101016/synthesis-and-evaluation-of-dual-crosslinked-alginate-microbeads
#10
Sami I Somo, Kelly Langert, Chin-Yu Yang, Marcella K Vaicik, Veronica Ibarra, Alyssa A Appel, Banu Akar, Ming-Huei Cheng, Eric M Brey
Alginate hydrogels have been investigated for a broad variety of medical applications. The ability to assemble hydrogels at neutral pH and mild temperatures makes alginate a popular choice for the encapsulation and delivery of cells and proteins. Alginate has been studied extensively for the delivery of islets as a treatment for type 1 diabetes. However, poor stability of the encapsulation systems after implantation remains a challenge. In this paper, alginate was modified with 2-aminoethyl methacrylate hydrochloride (AEMA) to introduce groups that can be photoactivated to generate covalent bonds...
October 31, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29099856/zn2-chelation-by-serum-albumin-improves-hexameric-zn2-insulin-dissociation-into-monomers-after-exocytosis
#11
José A G Pertusa, Trinidad León-Quinto, Genoveva Berná, Juan R Tejedo, Abdelkrim Hmadcha, Francisco J Bedoya, Franz Martín, Bernat Soria
β-cells release hexameric Zn2+-insulin into the extracellular space, but monomeric Zn2+-free insulin appears to be the only biologically active form. The mechanisms implicated in dissociation of the hexamer remain unclear, but they seem to be Zn2+ concentration-dependent. In this study, we investigate the influence of albumin binding to Zn2+ on Zn2+-insulin dissociation into Zn2+-free insulin and its physiological, methodological and therapeutic relevance. Glucose and K+-induced insulin release were analyzed in isolated mouse islets by static incubation and perifusion experiments in the presence and absence of albumin and Zn2+ chelators...
2017: PloS One
https://www.readbyqxmd.com/read/29095254/bibliometric-analysis-of-the-top-cited-articles-on-islet-transplantation
#12
Qiang-Hong Pu, Qiu-Ju Lyu, Huan Liu, Kai-Hua Fan
AIMS: To identify and characterize the top-cited articles in the field of islet transplantation. METHODS: We used the Science Citation Index Expanded database to identify the most frequently cited articles published after 1900. Articles were evaluated using the following characteristics: citation number, publication year, study design, references, country and institution of origin, authorship, and journal. Keyword analysis and citation networks were used to analyze research trends...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29078330/favorable-outcome-of-experimental-islet-xenotransplantation-without-immunosuppression-in-a-nonhuman-primate-model-of-diabetes
#13
Barbara Ludwig, Stefan Ludwig, Anja Steffen, Yvonne Knauf, Baruch Zimerman, Sophie Heinke, Susann Lehmann, Undine Schubert, Janine Schmid, Martina Bleyer, Uwe Schönmann, Clark K Colton, Ezio Bonifacio, Michele Solimena, Andreas Reichel, Andrew V Schally, Avi Rotem, Uriel Barkai, Helena Grinberg-Rashi, Franz-Josef Kaup, Yuval Avni, Peter Jones, Stefan R Bornstein
Transplantation of pancreatic islets for treating type 1 diabetes is restricted to patients with critical metabolic lability resulting from the need for immunosuppression and the shortage of donor organs. To overcome these barriers, we developed a strategy to macroencapsulate islets from different sources that allow their survival and function without immunosuppression. Here we report successful and safe transplantation of porcine islets with a bioartificial pancreas device in diabetic primates without any immune suppression...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29073149/intrapancreatic-injection-of-human-bone-marrow-derived-mesenchymal-stem-stromal-cells-alleviates-hyperglycemia-and-modulates-the-macrophage-state-in-streptozotocin-induced-type-1-diabetic-mice
#14
Norimitsu Murai, Hirokazu Ohtaki, Jun Watanabe, Zhifang Xu, Shun Sasaki, Kazumichi Yagura, Seiji Shioda, Shoichiro Nagasaka, Kazuho Honda, Masahiko Izumizaki
Type 1 diabetes mellitus is a progressive disease caused by the destruction of pancreatic β-cells, resulting in insulin dependency and hyperglycemia. While transplanted bone marrow-derived mesenchymal stem/stromal cells (BMMSCs) have been explored as an alternative therapeutic approach for diseases, the choice of delivery route may be a critical factor determining their sustainability. This study evaluated the effects of intrapancreatic and intravenous injection of human BMMSCs (hBMMSCs) in streptozotocin (STZ)-induced type 1 diabetic mouse model...
2017: PloS One
https://www.readbyqxmd.com/read/29068143/immunoisolation-of-murine-islet-allografts-in-vascularized-sites-through-conformal-coating-with-polyethylene-glycol
#15
Vita Manzoli, Chiara Villa, Allison L Bayer, Laura Morales, R Damaris Molano, Yvan Torrente, Camillo Ricordi, Jeffrey A Hubbell, Alice A Tomei
Islet encapsulation may allow transplantation without immunosuppression but thus far islets in large microcapsules transplanted in the peritoneal cavity failed to reverse diabetes in humans. We showed that islet transplantation in confined well-vascularized sites like the epididymal fat pad (EFP) improved graft outcomes, but only conformal coated (CC) islets can be implanted in these sites in curative doses. Here, we showed that CC using polyethylene glycol (PEG) and alginate (ALG) was not immunoisolating because of its high permselectivity and strong allogeneic T cell responses...
October 25, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29057561/pre-clinical-results-in-pig-to-non-human-primate-islet-xenotransplantation-using-anti-cd40-antibody-2c10r4-based-immunosuppression
#16
Jun-Seop Shin, Jong-Min Kim, Byoung-Hoon Min, Il Hee Yoon, Hyun Je Kim, Jung-Sik Kim, Yong-Hee Kim, Seong-Jun Kang, Jiyeon Kim, Hee-Jung Kang, Dong-Gyun Lim, Eung-Soo Hwang, Jongwon Ha, Sang-Joon Kim, Wan Beom Park, Chung-Gyu Park
BACKGROUND: Islet transplantation is an effective therapy for selected patients with type 1 diabetes with labile glycemic control and hypoglycemic unawareness, but donor organs are limited. Islet xenotransplantation using porcine islets will potentially solve this problem. Although successful proof of concept studies using clinically inapplicable anti-CD154 monoclonal antibody (mAb) in pig-to-non-human primate (NHP) islet xenotransplantation has been demonstrated by several groups worldwide, potentially clinically applicable anti-CD40 (2C10R4) mAb-based studies have not been reported...
October 22, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29051963/applications-of-particulate-oxygen-generating-substances-pogs-in-the-bioartificial-pancreas
#17
John P McQuilling, Sivanandane Sittadjody, Samuel Pendergraft, Alan C Farney, Emmanuel C Opara
Type-1 Diabetes (T1D) is a devastating autoimmune disorder which results in the destruction of beta cells within the pancreas. A promising treatment strategy for T1D is the replacement of the lost beta cell mass through implantation of immune-isolated microencapsulated islets referred to as the bioartificial pancreas. The goal of this approach is to restore blood glucose regulation and prevent the long-term comorbidities of T1D without the need for immunosuppressants. A major requirement in the quest to achieve this goal is to address the oxygen needs of islet cells...
October 20, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/29048258/selection-of-implantation-sites-for-transplantation-of-encapsulated-pancreatic-islets
#18
Haitao Zhu, Wenjing Li, Zhongwei Liu, Wenliang Li, Niuniu Chen, Linlin Lu, Wei Zhang, Zhen Wang, Bo Wang, Kaili Pan, Xiaoge Zhang, Guoqiang Chen
Pancreatic islet transplantation has been validated as a valuable therapy for type 1 diabetes mellitus patients with exhausted insulin treatment. However, this therapy remains limited by the shortage of donor and the requirement of lifelong immunosuppression. Islet encapsulation, as an available bioartificial pancreas (BAP), represents a promising approach to enable protecting islet grafts without or with minimal immunosuppression and possibly expanding the donor pool. In order to develop a clinically implantable BAP, some key aspects need to be taken into accounts: encapsulation material, capsule design and implantation site...
October 19, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/29046484/t-cells-expressing-chimeric-antigen-receptor-promote-immune-tolerance
#19
Antonio Pierini, Bettina P Iliopoulou, Heshan Peiris, Magdiel Pérez-Cruz, Jeanette Baker, Katie Hsu, Xueying Gu, Ping-Ping Zheng, Tom Erkers, Sai-Wen Tang, William Strober, Maite Alvarez, Aaron Ring, Andrea Velardi, Robert S Negrin, Seung K Kim, Everett H Meyer
Cellular therapies based on permanent genetic modification of conventional T cells have emerged as a promising strategy for cancer. However, it remains unknown if modification of T cell subsets, such as Tregs, could be useful in other settings, such as allograft transplantation. Here, we use a modular system based on a chimeric antigen receptor (CAR) that binds covalently modified mAbs to control Treg activation in vivo. Transient expression of this mAb-directed CAR (mAbCAR) in Tregs permitted Treg targeting to specific tissue sites and mitigated allograft responses, such as graft-versus-host disease...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29045546/characterization-of-adipose-tissue-product-quality-using-measurements-of-oxygen-consumption-rate
#20
Thomas M Suszynski, David A Sieber, Kathryn Mueller, Allen L Van Beek, Bruce L Cunningham, Jeffrey M Kenkel
Background: Fat grafting is a common procedure in plastic surgery but associated with unpredictable graft retention. Adipose tissue (AT) "product" quality is affected by the methods used for harvest, processing and transfer, which vary widely amongst surgeons. Currently, there is no method available to accurately assess the quality of AT. Objectives: In this study, we present a novel method for the assessment of AT product quality through direct measurements of oxygen consumption rate (OCR)...
October 13, 2017: Aesthetic Surgery Journal
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