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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
#1
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
#2
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
#3
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 (LMWDS) to control these initial reactions from the innate immune system. Fresh and cryopreserved hepatocytes were tested in an in vitro whole blood model using ABOcompatible blood. The ability to elicit IBMIR and the capacity of LMW-DS (100 µg/mL) to attenuate the degree of activation of the cascade systems was monitored...
July 22, 2016: Cell Transplantation
https://www.readbyqxmd.com/read/26996786/instant-blood-mediated-inflammatory-reaction-in-hepatocyte-transplantation-current-status-and-future-perspectives
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/26164512/-ultrasound-molecular-detection-of-immediately-blood-mediated-inflammatory-reaction-induced-by-%C3%A2-islets-transplantation-in-vitro
#11
Feng Gao, Qi Liang, Junling Li, Qiong Dong, Xiaoqian Ma, Wei Wang
OBJECTIVE: To study the feasibility of ultrasonic molecular imaging of immediately blood-mediated inflammatory reaction (IBMIR) in vitro.
 METHODS: IBMIR models in vitro were divided into 3 groups: Group A, no microbubbles were added; Group B, non-targeted micro-bubbles were added; Group C, Lys-Gly-Asp-Ser (KGDS)-targeted microbubbles (MBK) were added. The ultrasonic enhancement of IBMIR in loops by ultrasonic contrast imaging was evaluated.
 RESULTS: The contrast-enhanced US imaging did not show thrombus formation in the group A, whereas the thrombus was found in the Group B and C with a change in filling defects or ring enhancement, respectively...
June 2015: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/26084381/characterization-of-innate-immunity-in-an-extended-whole-blood-model-of-human-islet-allotransplantation
#12
Maria Hårdstedt, Susanne Lindblom, Alex Karlsson-Parra, Bo Nilsson, Olle Korsgren
The instant blood-mediated inflammatory reaction (IBMIR) has been studied in whole blood models of human allo-islet transplantation for short periods (<6 h). Beyond this time frame the innate response to intraportally transplanted islets is less well described. A novel whole blood model was applied to study blood-islet-graft interactions up to 48 h. Heparinized polyvinyl chloride tubing was sealed into small bags containing venous blood together with allogeneic human islets and exocrine tissue, respectively...
2016: Cell Transplantation
https://www.readbyqxmd.com/read/25818424/impact-of-an-autologous-oxygenating-matrix-culture-system-on-rat-islet-transplantation-outcome
#13
A Schaschkow, C Mura, W Bietiger, C Peronet, A Langlois, F Bodin, C Dissaux, C Bruant-Rodier, M Pinget, N Jeandidier, M T Juszczak, S Sigrist, E Maillard
Disruption of the pancreatic islet environment combined with the decrease in oxygen supply that occurs during isolation leads to poor islet survival. The aim of this study was to validate the benefit of using a plasma-based scaffold supplemented with perfluorodecalin to improve islet transplantation outcome. Rat islets were cultured in three conditions: i) control group, ii) plasma based-matrix (P-matrix), and iii) P-matrix supplemented with emulsified perfluorodecalin. After 24 h culture, matrix/cell contacts (Integrinβ1, p-FAK/FAK, p-Akt/Akt), survival (caspase 3, TUNEL, FDA/PI), function, and HIF-1α translocation were assessed...
June 2015: Biomaterials
https://www.readbyqxmd.com/read/25702898/dual-islet-transplantation-modeling-of-the-instant-blood-mediated-inflammatory-reaction
#14
B M Martin, K P Samy, M C Lowe, P W Thompson, J Cano, A B Farris, M Song, C R Dove, F V Leopardi, E A Strobert, J B Jenkins, B H Collins, C P Larsen, A D Kirk
Islet xenotransplantation is a potential treatment for diabetes without the limitations of tissue availability. Although successful experimentally, early islet loss remains substantial and attributed to an instant blood-mediated inflammatory reaction (IBMIR). This syndrome of islet destruction has been incompletely defined and characterization in pig-to-primate models has been hampered by logistical and statistical limitations of large animal studies. To further investigate IBMIR, we developed a novel in vivo dual islet transplant model to precisely characterize IBMIR as proof-of-concept that this model can serve to properly control experiments comparing modified xenoislet preparations...
May 2015: American Journal of Transplantation
https://www.readbyqxmd.com/read/25506683/xenotransplantation-of-porcine-islet-cells-as-a-potential-option-for-the-treatment-of-type-1-diabetes-in-the-future
#15
REVIEW
B Reichart, H Niemann, T Chavakis, J Denner, E Jaeckel, B Ludwig, G Marckmann, A Schnieke, R Schwinzer, J Seissler, R R Tönjes, N Klymiuk, E Wolf, S R Bornstein
Solid organ and cell transplantation, including pancreatic islets constitute the treatment of choice for chronic terminal diseases. However, the clinical use of allogeneic transplantation is limited by the growing shortage of human organs. This has prompted us to initiate a unique multi-center and multi-team effort to promote translational research in xenotransplantation to bring xenotransplantation to the clinical setting. Supported by the German Research Foundation, an interdisciplinary group of surgeons, internal medicine doctors, diabetologists, material sciences experts, immunologists, cell biologists, virologists, veterinarians, and geneticists have established a collaborative research center (CRC) focusing on the biology of xenogeneic cell, tissue, and organ transplantation...
January 2015: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/25375416/in-vitro-assessment-of-human-islet-vulnerability-to-instant-blood-mediated-inflammatory-reaction-ibmir-and-its-use-to-demonstrate-a-beneficial-effect-of-tissue-culture
#16
Raina D Ramnath, Elisa Maillard, Katherine Jones, Paul A Bateman, Stephen S J Hughes, Jane Gralla, Paul R Johnson, Derek W R Gray
Culture of human pancreatic islets is now routinely carried out prior to clinical islet allotransplantation, using conditions that have been developed empirically. One of the major causes of early islet destruction after transplantation is the process termed instant blood-mediated inflammatory reaction (IBMIR). The aim of this study was to develop in vitro methods to investigate IBMIR and apply them to the culture conditions used routinely in our human islet isolation laboratory. Freshly isolated or precultured (24 h, 48 h) human islets were incubated in either ABO-compatible allogeneic human blood or Hank's buffered salt solution (HBSS) for 1 h at 37°C...
2015: Cell Transplantation
https://www.readbyqxmd.com/read/24842781/control-of-ibmir-in-neonatal-porcine-islet-xenotransplantation-in-baboons
#17
W J Hawthorne, E J Salvaris, P Phillips, J Hawkes, D Liuwantara, H Burns, H Barlow, A B Stewart, S B Peirce, M Hu, A M Lew, S C Robson, M B Nottle, A J F D'Apice, P J O'Connell, P J Cowan
The instant blood-mediated inflammatory reaction (IBMIR) is a major obstacle to the engraftment of intraportal pig islet xenografts in primates. Higher expression of the galactose-α1,3-galactose (αGal) xenoantigen on neonatal islet cell clusters (NICC) than on adult pig islets may provoke a stronger reaction, but this has not been tested in the baboon model. Here, we report that WT pig NICC xenografts triggered profound IBMIR in baboons, with intravascular clotting and graft destruction occurring within hours, which was not prevented by anti-thrombin treatment...
June 2014: American Journal of Transplantation
https://www.readbyqxmd.com/read/24805247/do-cryopreserved-mesenchymal-stromal-cells-display-impaired-immunomodulatory-and-therapeutic-properties
#18
Guido Moll, Jessica J Alm, Lindsay C Davies, Lena von Bahr, Nina Heldring, Lillemor Stenbeck-Funke, Osama A Hamad, Robin Hinsch, Lech Ignatowicz, Matthew Locke, Helena Lönnies, John D Lambris, Yuji Teramura, Kristina Nilsson-Ekdahl, Bo Nilsson, Katarina Le Blanc
We have recently reported that therapeutic mesenchymal stromal cells (MSCs) have low engraftment and trigger the instant blood mediated inflammatory reaction (IBMIR) after systemic delivery to patients, resulting in compromised cell function. In order to optimize the product, we compared the immunomodulatory, blood regulatory, and therapeutic properties of freeze-thawed and freshly harvested cells. We found that freeze-thawed MSCs, as opposed to cells harvested from continuous cultures, have impaired immunomodulatory and blood regulatory properties...
September 2014: Stem Cells
https://www.readbyqxmd.com/read/24704666/the-role-of-the-alternative-complement-pathway-in-early-graft-loss-after-intraportal-porcine-islet-xenotransplantation
#19
Hee Jung Kang, Haneulnari Lee, Jeong-Mi Ha, Jae-Il Lee, Jun-Seop Shin, Ki-Yong Kim, Ji Yoon Park, Jung-Sik Kim, Sang Il Min, Chung-Gyu Park, Seong Hoe Park, Sang Joon Kim
BACKGROUND: Intraportal islet transplantation (ITx) causes instant blood-mediated inflammatory reaction (IBMIR), resulting in an early loss of transplanted islets. Porcine islets, transplanted intraportally into nonhuman primates (NHPs), induce complement activation, contributing to the development of IBMIR; however, the exact mechanism is not clear. METHODS: Complement activation were compared after incubation of purified adult porcine islets in 20% human serum with or without complement inhibitors, C1 esterase inhibitor (C1E-inh), anti-factor B, and purified human factor H...
May 27, 2014: Transplantation
https://www.readbyqxmd.com/read/24612163/liraglutide-protects-rin-m5f-%C3%AE-cells-by-reducing-procoagulant-tissue-factor-activity-and-apoptosis-prompted-by-microparticles-under-conditions-mimicking-instant-blood-mediated-inflammatory-reaction
#20
Céline Gleizes, Andrei Constantinescu, Malak Abbas, Houda Bouhadja, Fatiha Zobairi, Laurence Kessler, Florence Toti
Instant Blood-Mediated Inflammatory Reaction (IBMIR) occurs at the vicinity of transplanted islets immediately after intraportal infusion and is characterized by cytokine secretion, tissue factor (TF) expression, and ß cell loss. Microparticles (MPs) are cellular effectors shed from the plasma membrane of apoptotic cells. Modulation of the properties of ß cell-derived MPs by liraglutide was assessed in a cellular model designed to mimic IBMIR oxidative and inflammatory conditions. Rin-m5f rat β cells were stimulated by H2 O2 or a combination of IL-1β and TNF-α...
July 2014: Transplant International: Official Journal of the European Society for Organ Transplantation
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