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https://www.readbyqxmd.com/read/29356341/cryopreserved-neonatal-hepatocytes-may-be-a-source-for-transplantation-evaluation-of-functionality-towards-clinical-use
#1
Charlotte A Lee, Anil Dhawan, Valeria Iansante, Sharon Lehec, Shirin Elizabeth Khorsandi, Celine Filippi, Simon Walker, Raquel Fernandez-Dacosta, Nigel Heaton, Sanjay Bansal, Ragai R Mitry, Emer Fitzpatrick
Neonatal livers are a potential source of good quality hepatocytes for clinical transplantation. We compared viability and function of neonatal and adult hepatocytes, and report their clinical use both intra-portally and in alginate microbeads. Following isolation from donor livers, hepatocyte function was assessed using albumin, alpha-1 antitrypsin and factor VII. Metabolic function was investigated by measuring resorufin conjugation, ammonia metabolism, UGT enzyme activity and cytochrome P450 function following induction...
January 21, 2018: Liver Transplantation
https://www.readbyqxmd.com/read/29178588/early-barriers-to-neonatal-porcine-islet-engraftment-in-a-dual-transplant-model
#2
K P Samy, R P Davis, Q Gao, B M Martin, M Song, J Cano, A B Farris, A McDonald, E K Gall, C R Dove, F V Leopardi, T How, K D Williams, G R Devi, B H Collins, A D Kirk
Porcine islet xenografts have the potential to provide an inexhaustible source of islets for β cell replacement. Proof-of-concept has been established in nonhuman primates. However, significant barriers to xenoislet transplantation remain, including, the poorly understood instant blood mediated inflammatory reaction (IBMIR), and a thorough understanding of early xeno-specific immune responses. A paucity of data exist comparing xeno-specific immune responses to allo-islet responses in primates. We recently developed a dual islet transplant model, which enables direct histological comparison of early engraftment immunobiology...
November 25, 2017: American Journal of 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
#3
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
#4
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/28736020/mechanism-for-the-instant-blood-mediated-inflammatory-reaction-in-rat-islet-transplantation
#5
Y Cheng, B Wang, H Li, N Zhao, Y Liu
OBJECTIVE: The purpose of this study was to investigate the mechanisms involved in the development of instant blood-mediated inflammatory reaction (IBMIR) triggered by pancreatic islet transplantation in an in vitro system. MATERIALS AND METHODS: Pancreatic islets were prepared and blood was taken from male and female Wistar rats. An in vitro heparinized tubing loop model on a rocking device that was placed in a 37°C incubator was used to generate blood flow inside the loops...
July 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28558297/mri-sensitive-contrast-agent-with-anticoagulant-activity-for-surface-camouflage-of-transplanted-pancreatic-islets
#6
Yong Hwa Hwang, Min Jun Kim, Dong Yun Lee
Pancreatic islet implantation in the liver is a promising approach for diabetes therapy. However, 70% of the islet mass fails to be engrafted in the liver due to the instant blood-mediated inflammatory reactions (IBMIR) resulting from direct contact between islet cells and the bloodstream. To overcome this issue, direct monitoring is very important for establishing prognosis after islet cell therapy. Here we established a new type of MR contrast agent with anticoagulant activity via heparin-immobilized superparamagnetic iron oxide (HSPIO)...
May 23, 2017: Biomaterials
https://www.readbyqxmd.com/read/28247506/the-effect-of-hypoxia-on-free-and-encapsulated-adult-porcine-islets-an-in-vitro-study
#7
Sudhakar Muthyala, Susan Safley, Kereen Gordan, Graham Barber, Collin Weber, Athanassios Sambanis
BACKGROUND: Adult porcine islets (APIs) constitute a promising alternative to human islets in treating type 1 diabetes. The intrahepatic site has been used in preclinical primate studies of API xenografts; however, an estimated two-thirds of donor islets are destroyed after intraportal infusion due to a number of factors, including the instant blood-mediated inflammatory reaction (IBMIR), immunosuppressant toxicity, and poor reestablishment of extracellular matrix connections. Intraperitoneal (ip) transplantation of non-vascularized encapsulated islets offers several advantages over intrahepatic transplantation of free islets, including avoidance of IBMIR, immunoprotection, accommodation of a larger graft volume, and reduced risk of hemorrhage...
January 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28109023/intraportal-islet-transplantation-the-impact-of-the-liver-microenvironment
#8
REVIEW
Vaihere Delaune, Thierry Berney, Stéphanie Lacotte, Christian Toso
The portal vein remains the preferred site for pancreatic islet transplantation due to its easy access and low morbidity. However, despite great progress in isolation and transplantation protocols over the past few years, it is still associated with the early loss of some 50-70% of transplanted islets. The complex liver microenvironment itself presumably plays an important role in this loss. The present review focuses on the specifics of the liver microenvironment, notably the localized hepatic ischemia/reperfusion injury following transplantation, the low oxygenation of the portal vein, the instant blood-mediated inflammatory reaction, the endogenous liver immune system, and the gut-liver axis, and how they can each have an impact on the transplanted islets...
March 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28069642/%C3%AE-1-antitrypsin-enhances-islet-engraftment-by-suppression-of-instant-blood-mediated-inflammatory-reaction
#9
Jingjing Wang, Zhen Sun, Wenyu Gou, David B Adams, Wanxing Cui, Katherine A Morgan, Charlie Strange, Hongjun Wang
Islet cell transplantation has limited effectiveness because of an instant blood-mediated inflammatory reaction (IBMIR) that occurs immediately after cell infusion and leads to dramatic β-cell death. In intraportal islet transplantation models using mouse and human islets, we demonstrated that α-1 antitrypsin (AAT; Prolastin-C), a serine protease inhibitor used for the treatment of AAT deficiency, inhibits IBMIR and cytokine-induced inflammation in islets. In mice, more diabetic recipients reached normoglycemia after intraportal islet transplantation when they were treated with AAT compared with mice treated with saline...
April 2017: Diabetes
https://www.readbyqxmd.com/read/27938471/human-recombinant-antithrombin-atryn-%C3%A2-administration-improves-survival-and-prevents-intravascular-coagulation-after-intraportal-islet-transplantation-in-a-piglet-model
#10
Valery Gmyr, Caroline Bonner, Ericka Moerman, Antoine Tournoys, Nathalie Delalleau, Audrey Quenon, Julien Thevenet, Mikael Chetboun, Julie Kerr-Conte, François Pattou, Thomas Hubert, Merce Jourdain
Human islet transplantation is a viable treatment option for type 1 diabetes mellitus (T1DM). However, pancreatic islet inflammation after transplantation induced by innate immune responses is likely to hinder graft function. This is mediated by incompatibility between islets and the blood interface, known as instant blood-mediated inflammatory reaction (IBMIR). Herein we hypothesized that portal venous administration of islet cells with human recombinant antithrombin (ATryn®), a serine protease inhibitor (serpin), which plays a central role in the physiological regulation of coagulation and exerts indirect anti-inflammatory activities, may offset coagulation abnormalities such as disseminated intravascular coagulation (DIC) and IBMIR...
February 16, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/27766032/a-metabolomic-approach-1-h-hrmas-nmr-spectroscopy-supported-by-histology-to-study-early-post-transplantation-responses-in-islet-transplanted-livers
#11
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
https://www.readbyqxmd.com/read/27500267/characterizing-the-mechanistic-pathways-of-the-instant-blood-mediated-inflammatory-reaction-in-xenogeneic-neonatal-islet-cell-transplantation
#12
David Liuwantara, Yi Vee Chew, Emmanuel J Favaloro, Joanne M Hawkes, Heather L Burns, Philip J O'Connell, Wayne J Hawthorne
INTRODUCTION: The instant blood-mediated inflammatory reaction (IBMIR) causes major loss of islets after transplantation and consequently represents the initial barrier to survival of porcine neonatal islet cell clusters (NICC) after xenotransplantation. METHODS: This study used novel assays designed to characterize the various immunologic components responsible for xenogeneic IBMIR to identify initiators and investigate processes of IBMIR-associated coagulation, complement activation and neutrophil infiltration...
June 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27452808/control-of-ibmir-induced-by-fresh-and-cryopreserved-hepatocytes-by-low-molecular-weight-dextran-sulfate-versus-heparin
#13
Elisabet Gustafson, Sana Asif, Huda Kozarcanin, Graciela Elgue, Staffan Meurling, Kristina N Ekdahl, Bo Nilsson
Rapid destruction of hepatocytes after hepatocyte transplantation has hampered the application of this procedure clinically. The instant blood-mediated inflammatory reaction (IBMIR) is a plausible underlying cause for this cell loss. The present study was designed to evaluate the capacity of low molecular weight dextran sulfate (LMW-DS) to control these initial reactions from the innate immune system. Fresh and cryopreserved hepatocytes were tested in an in vitro whole-blood model using ABO-compatible blood...
January 24, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/26996786/instant-blood-mediated-inflammatory-reaction-in-hepatocyte-transplantation-current-status-and-future-perspectives
#14
REVIEW
Charlotte A Lee, Anil Dhawan, Richard A Smith, Ragai R Mitry, Emer Fitzpatrick
Hepatocyte transplantation (HT) is emerging as a promising alternative to orthotopic liver transplantation (OLT) in patients with certain liver-based metabolic disease and acute liver failure. Hepatocytes are generally infused into the portal venous system, from which they migrate into the liver cell plates of the native organ. One of the major hurdles to the sustained success of this therapy is early cell loss, with up to 70% of hepatocytes lost immediately following infusion. This is largely thought to be due to the instant blood-mediated inflammatory reaction (IBMIR), resulting in the activation of complement and coagulation pathways...
2016: Cell Transplantation
https://www.readbyqxmd.com/read/26988899/initial-in-vitro-studies-on-tissues-and-cells-from-gtko-cd46-neugcko-pigs
#15
Whayoung Lee, Hidetaka Hara, Mohamed B Ezzelarab, Hayato Iwase, Rita Bottino, Cassandra Long, Jagdeece Ramsoondar, David Ayares, David K C Cooper
BACKGROUND: The impact that the absence of expression of NeuGc in pigs might have on pig organ or cell transplantation in humans has been studied in vitro, but only using red blood cells (pRBCs) and peripheral blood mononuclear cells (pPBMCs) as the target cells for immune assays. We have extended this work in various in vitro models and now report our initial results. METHODS: The models we have used involve GTKO/hCD46 and GTKO/hCD46/NeuGcKO pig aortas and corneas, and pRBCs, pPBMCs, aortic endothelial cells (pAECs), corneal endothelial cells (pCECs), and isolated pancreatic islets...
March 2016: Xenotransplantation
https://www.readbyqxmd.com/read/26857703/endoscopic-biopsy-of-islet-transplants-in-the-gastric-submucosal-space-provides-evidence-of-islet-graft-rejection-in-diabetic-pigs
#16
COMPARATIVE STUDY
Takayuki Tanaka, Minoru Fujita, Rita Bottino, Jon D Piganelli, Kevin McGrath, Jiang Li, Whayoung Lee, Hayato Iwase, Martin Wijkstrom, Suzanne Bertera, Cassandra Long, Douglas Landsittel, Ken Haruma, David K C Cooper, Hidetaka Hara
Transplantation of islets into the gastric submucosal space (GSMS) has several advantages (e.g., avoidance of the instant blood-mediated inflammatory response [IBMIR], ability to biopsy). The aim of this study was to determine whether endoscopic biopsy of islet allografts transplanted into the GSMS in diabetic pigs can provide histopathological and immunohistochemical information that correlates with the clinical course (e.g.,, blood glucose level, insulin requirement). Islet allografts (Group1: 10,000 kIEq /kg [n = 4]; Group2: 15,000 kIEq /kg [n = 2]) were transplanted into the GSMS of diabetic pigs under immunosuppression...
2016: Islets
https://www.readbyqxmd.com/read/26676803/developmental-endothelial-locus-1-modulates-platelet-monocyte-interactions-and-instant-blood-mediated-inflammatory-reaction-in-islet-transplantation
#17
Ioannis Kourtzelis, Klara Kotlabova, Jong-Hyung Lim, Ioannis Mitroulis, Anaisa Ferreira, Lan-Sun Chen, Bettina Gercken, Anja Steffen, Elisabeth Kemter, Anne Klotzsche-von Ameln, Claudia Waskow, Kavita Hosur, Antonios Chatzigeorgiou, Barbara Ludwig, Eckhard Wolf, George Hajishengallis, Triantafyllos Chavakis
Platelet-monocyte interactions are strongly implicated in thrombo-inflammatory injury by actively contributing to intravascular inflammation, leukocyte recruitment to inflamed sites, and the amplification of the procoagulant response. Instant blood-mediated inflammatory reaction (IBMIR) represents thrombo-inflammatory injury elicited upon pancreatic islet transplantation (islet-Tx), thereby dramatically affecting transplant survival and function. Developmental endothelial locus-1 (Del-1) is a functionally versatile endothelial cell-derived homeostatic factor with anti-inflammatory properties, but its potential role in IBMIR has not been previously addressed...
April 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/26565566/apt070-mirococept-a-membrane-localizing-c3-convertase-inhibitor-attenuates-early-human-islet-allograft-damage-in-vitro-and-in-vivo-in-a-humanized-mouse-model
#18
Fang Xiao, Liang Ma, Min Zhao, Richard A Smith, Guocai Huang, Peter M Jones, Shanta Persaud, Attilio Pingitore, Anthony Dorling, Robert Lechler, Giovanna Lombardi
BACKGROUND AND PURPOSE: A major obstacle to islet cell transplantation is the early loss of transplanted islets resulting from the instant blood-mediated inflammation reaction (IBMIR). The activation of complement pathways plays a central role in IBMIR. The aim of this study was to test the inhibitory effect of "painting" human islets with APT070, a membrane-localizing C3 convertase inhibitor, on inflammation evoked by exposure to human serum in vitro and by transplantation in vivo in a humanized diabetic mouse model...
February 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/26306450/regulation-of-instant-blood-mediated-inflammatory-reaction-ibmir-in-pancreatic-islet-xeno-transplantation-points-for-therapeutic-interventions
#19
REVIEW
Ioannis Kourtzelis, Peetra U Magnusson, Klara Kotlabova, John D Lambris, Triantafyllos Chavakis
Xeno-transplantation of pancreatic islets represents a promising therapeutic alternative for the treatment of type 1 diabetes mellitus. However, potent innate immune responses induced shortly after the transplantation of donor islets to the recipient, comprising the Instant Blood Mediated Immune Reaction (IBMIR), exert detrimental actions on islet graft function. The coagulation and complement cascades together with the leukocyte and platelet populations are the major players in IBMIR. This innate immune attack affects dramatically islet integrity and leads to significant loss of function of the xenograft...
2015: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/26179209/in-vitro-exposure-of-pig-neonatal-isletlike-cell-clusters-to-human-blood
#20
Santosh Nagaraju, Suzanne Bertera, Takayuki Tanaka, Hidetaka Hara, Gina R Rayat, Martin Wijkstrom, David Ayares, Massimo Trucco, David K C Cooper, Rita Bottino
BACKGROUND: Pig islet grafts have been successful in treating diabetes in animal models. One remaining question is whether neonatal pig isletlike cell clusters (NICC) are resistant to the early loss of islets from the instant blood-mediated inflammatory reaction (IBMIR). METHODS: Neonatal isletlike cell clusters were harvested from three groups of piglets-(i) wild-type (genetically unmodified), (ii) α1,3-galactosyltransferase gene-knockout (GTKO)/CD46, and (iii) GTKO/CD46/CD39...
July 2015: Xenotransplantation
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