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Islet transplantation

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https://www.readbyqxmd.com/read/28432571/cell-therapy-for-type-1-diabetes-current-and-future-strategies
#1
REVIEW
Yasaman Aghazadeh, Maria Cristina Nostro
PURPOSE OF THE REVIEW: Type 1 diabetes (T1D) is defined by an autoimmune destruction of insulin producing β-cells located in the endocrine part of the pancreas, the islets of Langerhans. As exogenous insulin administration fails at preventing severe complications associated with this disease, cell replacement therapies are being considered as a means to treat T1D. The purpose of this manuscript is to review the challenges associated with current strategies and discuss the potential of stem cell therapy for the treatment of T1D...
June 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28424327/rig-i-mavs-and-sting-signaling-promote-gut-integrity-during-irradiation-and-immune-mediated-tissue-injury
#2
Julius C Fischer, Michael Bscheider, Gabriel Eisenkolb, Chia-Ching Lin, Alexander Wintges, Vera Otten, Caroline A Lindemans, Simon Heidegger, Martina Rudelius, Sébastien Monette, Kori A Porosnicu Rodriguez, Marco Calafiore, Sophie Liebermann, Chen Liu, Stefan Lienenklaus, Siegfried Weiss, Ulrich Kalinke, Jürgen Ruland, Christian Peschel, Yusuke Shono, Melissa Docampo, Enrico Velardi, Robert R Jenq, Alan M Hanash, Jarrod A Dudakov, Tobias Haas, Marcel R M van den Brink, Hendrik Poeck
The molecular pathways that regulate the tissue repair function of type I interferon (IFN-I) during acute tissue damage are poorly understood. We describe a protective role for IFN-I and the RIG-I/MAVS signaling pathway during acute tissue damage in mice. Mice lacking mitochondrial antiviral-signaling protein (MAVS) were more sensitive to total body irradiation- and chemotherapy-induced intestinal barrier damage. These mice developed worse graft-versus-host disease (GVHD) in a preclinical model of allogeneic hematopoietic stem cell transplantation (allo-HSCT) than did wild-type mice...
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28420418/adult-muscle-derived-stem-cells-engraft-and-differentiate-into-insulin-expressing-cells-in-pancreatic-islets-of-diabetic-mice
#3
Violeta Mitutsova, Wendy Wai Yeng Yeo, Romain Davaze, Celine Franckhauser, El-Habib Hani, Syahril Abdullah, Patrice Mollard, Marie Schaeffer, Anne Fernandez, Ned J C Lamb
BACKGROUND: Pancreatic beta cells are unique effectors in the control of glucose homeostasis and their deficiency results in impaired insulin production leading to severe diabetic diseases. Here, we investigated the potential of a population of nonadherent muscle-derived stem cells (MDSC) from adult mouse muscle to differentiate in vitro into beta cells when transplanted as undifferentiated stem cells in vivo to compensate for beta-cell deficiency. RESULTS: In vitro, cultured MDSC spontaneously differentiated into insulin-expressing islet-like cell clusters as revealed using MDSC from transgenic mice expressing GFP or mCherry under the control of an insulin promoter...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28417501/d-dimer-level-in-association-with-humoral-responses-negatively-correlates-with-survival-of-porcine-islet-grafts-in-non-human-primates-with-immunosuppression
#4
Hee Jung Kang, Haneulnari Lee, Eun Mi Park, Jong-Min Kim, Byoung-Hoon Min, Chung-Gyu Park
BACKGROUND: Several immunosuppression (IS) regimens achieve long-term graft survival in non-human primates (NHPs) after porcine islet transplantation (PITx), but their success rates vary. To understand the mechanism of graft loss, we investigated the relationships between graft survival and humoral or inflammatory responses for maintenance IS in NHPs after PITx. METHODS: Islets purified from adult wild-type pigs were intraportally transplanted into streptozotocin-induced diabetic rhesus monkeys...
April 18, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28412348/closed-channel-culture-system-for-efficient-and-reproducible-differentiation-of-human-pluripotent-stem-cells-into-islet-cells
#5
Kunio Hirano, Shuhei Konagaya, Alexander Turner, Yuichiro Noda, Shigeru Kitamura, Hidetoshi Kotera, Hiroo Iwata
Human pluripotent stem cells (hPSCs) are thought to be a promising cell-source solution for regenerative medicine due to their indefinite proliferative potential and ability to differentiate to functional somatic cells. However, issues remain with regard to achieving reproducible differentiation of cells with the required functionality for realizing human transplantation therapies and with regard to reducing the potential for bacterial or fungal contamination. To meet these needs, we have developed a closed-channel culture device and corresponding control system...
April 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28400333/umbilical-cord-mesenchymal-stem-cells-are-able-to-undergo-differentiation-into-functional-islet-like-cells-in-type-2-diabetic-tree-shrews
#6
Xing-Hua Pan, Xia Huang, Guang-Ping Ruan, Rong-Qing Pang, Qiang Chen, Jin-Xiang Wang, Jie He, Jing Zhao, Xue-Min Cai, Na Zhao, Yi Chen, Xiang-Qing Zhu
Islet transplantation is arguably one of the most promising strategies to treat patients suffering with diabetes mellitus. However, a combination of a lack of donors and chronic immune rejection limit clinical applications. Here, we evaluated the efficacy of cell therapy using islet-like cells differentiated from umbilical cord mesenchymal stem cells (UC-MSCs) of tree shrews for the treatment of type 2 diabetes. Enhanced green fluorescent protein (eGFP) labeled UC-MSCs were directly injected into type 2 diabetic tree shrews, where UC-MSC differentiated into functional islet-like cells and alleviated disease severity, as evidenced by improved biochemical features and reduced concentrations of inflammatory cytokines...
April 8, 2017: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/28397351/the-resurgence-of-xenotransplantation
#7
Peter J Cowan, A Joseph Tector
There has been an upsurge of interest in xenotransplantation in recent years. This resurgence can attributed to a combination of factors. First, there has been a dramatic improvement in efficacy in several preclinical models, with maximum xenograft survival times increasing to 950 days for islets, 945 days for hearts, and 310 days for kidneys. Second, the rapid development of genome editing technology (particularly the advent of CRISPR/Cas9) has revolutionized the capacity to generate new donor pigs with multiple protective genetic modifications; what once took many years to achieve can now be performed in months, with much greater precision and scope...
April 11, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28397308/improvement-of-isolated-caprine-islet-survival-and-functionality-in-vitro-by-enhancing-of-pdx1-gene-expression
#8
Homayoun Hani, Zeenathul Nazariah Allaudin, Mohd-Azmi Mohd-Lila, Kazhal Sarsaifi, Mina Rasouli, Yew Joon Tam, Tengku-Azmi Tengku-Ibrahim, Abas Mazni Othman
BACKGROUND: Dead islets replaced with viable islets are a promising offer to restore normal insulin production to a person with diabetes. The main reason for establishing a new islet source for transplantation is the insufficiency of human donor pancreas while using xenogeneic islets perhaps assists this problem. The expression of PDX1 is essential for the pancreas expansion. In mature β-cells, PDX1 has several critical roles such as glucose sensing, insulin synthesis, and insulin secretion...
April 11, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28394196/reactive-oxygen-species-shielding-hydrogel-for-the-delivery-of-adherent-and-nonadherent-therapeutic-cell-types
#9
Bryan R Dollinger, Mukesh K Gupta, John R Martin, Craig L Duvall
Cell therapies suffer from poor survival post-transplant due to placement into hostile implant sites characterized by host immune response and innate production of high levels of reactive oxygen species (ROS). We hypothesized that cellular encapsulation within an injectable, antioxidant hydrogel would improve viability of cells exposed to high oxidative stress. To test this hypothesis, we applied a dual thermo- and ROS-responsive hydrogel comprising the ABC triblock polymer poly[(propylene sulfide)-block-(N,N-dimethyl acrylamide)-block-(N-isopropylacrylamide)] (PPS135-b-PDMA152-b-PNIPAAM225, PDN)...
April 7, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28390107/post-transplant-lymphoproliferative-disorder-following-clinical-islet-transplantation-report-of-the-first-two-cases
#10
Anthea Peters, Tolu Olateju, Jean Deschenes, Santosh H Shankarnarayan, Neil Chua, A M James Shapiro, Peter Senior
We report the first two cases of post-transplant lymphoproliferative disorder (PTLD) in recipients of islet transplants worldwide. First, a 44-year old recipient of 3 islet infusions developed PTLD 80 months after his initial transplant, presenting with abdominal pain and diffuse terminal ileum thickening on imaging. He was treated with surgical excision, reduction of immunosuppression and rituximab. Seven months later he developed central nervous system PTLD, presenting with vertigo and diplopia; immunosuppression was discontinued, resulting in graft loss, and he was given high-dose methotrexate and consolidative autologous stem cell transplant...
April 8, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28386318/pax4-promotes-pdx1-induced-differentiation-of-mesenchymal-stem-cells-into-insulin-secreting-cells
#11
Lifa Xu, Congjing Xu, Shuping Zhou, Xueke Liu, Jian Wang, Xinkuang Liu, Suping Qian, Yingru Xin, Yi Gao, Yongqiang Zhu, Xiaolong Tang
A shortage of postmortem pancreatic tissue for islet isolation impedes the application of cell replacement therapy in patients with diabetes. As an alternative for islet cell transplantation, transcription factors, including PDX1, PAX4, and neurogenin-3, that aid in the formation of insulin-producing β cells during development have been investigated. The present study evaluated the effects of PAX4 and PDX1 on the differentiation of mesenchymal stem cells (MSCs) into insulin-producing β-like cells in vitro using recombinant adenoviruses carrying PDX1 or PDX1 plus PAX4...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28385600/mesenchymal-stem-cells-and-differentiated-insulin-producing-cells-are-new-horizons-for-pancreatic-regeneration-in-type-i-diabetes-mellitus
#12
Ayat M Domouky, Ashraf S Hegab, Amal Al-Shahat, Nermin Raafat
BACKGROUND: Diabetes mellitus has become the third human killer following cancer and cardiovascular disease. Millions of patients, often children, suffer from type 1 diabetes (T1D). Stem cells created hopes to regenerate damaged body tissues and restore their function. AIM: This work aimed at clarifying and comparing the therapeutic potential of differentiated and non-differentiated mesenchymal stem cells (MSCs) as a new line of therapy for T1D. METHODS: 40 Female albino rats divided into group I (control): 10 rats and group II (diabetic), III and IV, 10 rats in each, were injected with streptozotocin (50mg/kg body weight)...
April 3, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28385584/a-study-of-the-clinical-utility-of-a-20-minute-secretin-stimulated-endoscopic-pancreas-function-test-and-performance-according-to-clinical-variables
#13
Luis F Lara, Morihito Takita, James S Burdick, Daniel C DeMarco, Ronnie R Pimentel, Tolga Erim, Marlon F Levy
BACKGROUND & AIMS: Direct pancreas juice testing of bicarbonate, lipase, or trypsin after stimulation by secretin or cholecystokinin (CCK) is used to determine exocrine function, a surrogate for diagnosing chronic pancreatitis (CP). Endoscopic pancreas function tests (ePFT) where a peak bicarbonate concentration (PBC) ≥80 mEq/L in pancreas juice is considered normal are now used more frequently. In this ePFT aspirates start 35 minutes after secretin administration because pancreas output peaks 30 minutes after secretagogue administration...
April 3, 2017: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/28371625/injectable-and-inherently-vascularizing-semi-interpenetrating-polymer-network-for-delivering-cells-to-the-subcutaneous-space
#14
Redouan Mahou, David K Y Zhang, Alexander E Vlahos, Michael V Sefton
Injectable hydrogels are suitable for local cell delivery to the subcutaneous space, but the lack of vasculature remains a limiting factor. Previously we demonstrated that biomaterials containing methacrylic acid promoted vascularization. Here we report the preparation of a semi-interpenetrating polymer network (SIPN), and its evaluation as an injectable carrier to deliver cells and generate blood vessels in a subcutaneous implantation site. The SIPN was prepared by reacting a blend of vinyl sulfone-terminated polyethylene glycol (PEG-VS) and sodium polymethacrylate (PMAA-Na) with dithiothreitol...
March 24, 2017: Biomaterials
https://www.readbyqxmd.com/read/28368485/measurement-of-pro-islet-amyloid-polypeptide-1-48-in-diabetes-and-islet-transplants
#15
Jaques A Courtade, Agnieszka M Klimek-Abercrombie, Yi-Chun Chen, Nirja Patel, Phoebe Y T Lu, Cate Speake, Paul C Orban, Behzad Najafian, Graydon Meneilly, Carla J Greenbaum, Garth L Warnock, Constadina Panagiotopoulos, C Bruce Verchere
Context: Islet amyloid is a feature of beta cell failure in type 2 diabetes (T2D) and type 1 diabetic (T1D) recipients of islet transplants. Islet amyloid contains islet amyloid polypeptide (IAPP; amylin), a circulating peptide that is produced in beta cells by processing of its precursor, proIAPP1-67, via an intermediate form, proIAPP1-48. Elevated proinsulin to C-peptide ratios in the plasma of persons with diabetes suggest defects in beta cell prohormone processing. Objective: Determine whether plasma levels of precursor forms of IAPP are elevated in diabetes...
March 24, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28363269/establishing-a-large-animal-model-for-in-vivo-reprogramming-of-bile-duct-cells-into-insulin-secreting-cells-to-treat-diabetes
#16
Caitlin Marie Hill, Anannya Banga, Juan E Abrahante, Ce Yuan, Lucas A Mutch, Jody Janecek, Timothy O'Brien, Melanie L Graham, James Dutton
Type I diabetes manifests in autoimmune destruction of beta cells requiring metabolic management with an exogenous replacement source of insulin, either by repeated injection of recombinant insulin or by transplantation of allogenic islets from cadaveric donors. Both of these approaches have severe limitations. Repeated insulin injection requires intensive blood glucose monitoring, is expensive, and is associated with decreased quality of life measures. Islet transplant, while highly effective, is severely limited by shortage of donor organs...
March 31, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28360408/senescence-of-pancreas-in-middle-aged-rats-with-normal-vascular-function
#17
Mohamad Kassem, Zahid Rasul Niazi, Malak Abbas, Ali El Habhab, Guillaume Kreutter, Sonia Khemais-Benkhiat, Cyril Auger, Maria-Cristina Antal, Valérie B Schini-Kerth, Florence Toti, Laurence Kessler
BACKGROUND In organ transplantation, particularly pancreas transplantation, donor age is a determinant factor for graft survival. Physiological aging is crucial in the progressive deterioration of organs in adulthood. We compared the senescence and function features of pancreas and vascular tissues in young rats and middle-aged rats. MATERIAL AND METHODS Islet morphology and the area of cells secreting insulin or glucagon was investigated using immunohistology in young rats (12 weeks) and middle-aged rats (52 weeks) (n=8)...
March 31, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28360105/demethylation-of-induced-pluripotent-stem-cells-from-type-1-diabetic-patients-enhances-differentiation-into-functional-pancreatic-%C3%AE-cells
#18
Gohar S Manzar, Eun-Mi Kim, Nicholas Zavazava
Type 1 diabetes (T1D) can be managed by transplanting either the whole pancreas or isolated pancreatic islets. However, cadaveric pancreas is scarcely available for clinical use, limiting this approach. As such, there is a great need to identify alternative sources of clinically usable pancreatic tissues. Here, we used induced pluripotent stem (iPS) cells derived from patients with T1D to generate glucose-responsive, insulin-producing cells (IPCs) via 3D culture. Initially, T1D iPS cells were resistant to differentiation, but transient demethylation treatment significantly enhanced IPC yield...
March 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28358858/a-preclinical-evaluation-of-alternative-site-for-islet-allotransplantation
#19
Chengshi Wang, Xiaojiong Du, Sirong He, Yujia Yuan, Pengfei Han, Dan Wang, Younan Chen, Jingping Liu, Bole Tian, Guang Yang, Shounan Yi, Fabao Gao, Zhihui Zhong, Hongxia Li, Jingqiu Cheng, Yanrong Lu
The bone marrow cavity (BMC) has recently been identified as an alternative site to the liver for islet transplantation. This study aimed to compare the BMC with the liver as an islet allotransplantation site in diabetic monkeys. Diabetes was induced in Rhesus monkeys using streptozocin, and the monkeys were then divided into the following three groups: Group1 (islets transplanted in the liver with immunosuppressant), Group 2 (islets transplanted in the tibial BMC), and Group 3 (islets transplanted in the tibial BMC with immunosuppressant)...
2017: PloS One
https://www.readbyqxmd.com/read/28358727/salvage-islet-auto-transplantation-after-relaparatomy
#20
Gianpaolo Balzano, Rita Nano, Paola Maffi, Alessia Mercalli, Raffaelli Melzi, Francesca Aleotti, Francesca Gavazzi, Cesare Berra, Francesco De Cobelli, Massimo Venturini, Paola Magistretti, Marina Scavini, Giovanni Capretti, Alessandro Del Maschio, Antonio Secchi, Alessandro Zerbi, Massimo Falconi, Lorenzo Piemonti
BACKGROUND: To assess feasibility, safety and metabolic outcome of islet auto transplantation (IAT) in patients undergoing completion pancreatectomy because of sepsis or bleeding following pancreatic surgery. METHODS: From November 2008 to October 2016, 22 patients were candidates to salvage IAT during emergency relaparotomy because of postpancreatectomy sepsis (n=11) or bleeding (n=11). Feasibility, efficacy, and safety of salvage IAT were compared to those documented in a cohort of 36 patients who were candidate to simultaneous IAT during nonemergency preemptive completion pancreatectomy through the pancreaticoduodenectomy...
March 29, 2017: Transplantation
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