The DOI matches its Crossref record.
Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation
Abstract
Background Intraportal transplantation of pancreatic islets offers improved glycaemic control and insulin independence in type 1 diabetes mellitus, but intraportal thrombosis remains a possible complication. The thrombotic reaction may explain why graft loss occurs and islets from more than one donor are needed, since contact between human islets and ABO-compatible blood in vitro triggers a thrombotic reaction that damages the islets. We investigated the possible mechanism and treatment of such thrombotic reactions. Methods Coagulation activation and islet damage were monitored in four patients undergoing clinical islet transplantation according to a modified Edmonton protocol. Expression of tissue factor (TF) in the islet preparations was investigated by immunohistochemistry, immunoprecipitation, electron microscopy, and RT-PCR. To assess TF activity in purified islets, human islets were mixed with non-anticoagulated ABO-compatible blood in tubing loops coated with heparin. Findings Coagulation activation and subsequent release of insulin were found consistently after clinical islet transplantation, even in the absence of signs of intraportal thrombosis. The endocrine, but not the exocrine, cells of the pancreas were found to synthesise and secrete active TF. The clotting reaction triggered by pancreatic islets in vitro could be abrogated by blocking the active site of TF with specific antibodies or site-inactivated factor VIIa, a candidate drug for inhibition of TF activity…
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“One consequence of this direct blood contact is an immune response called the instant blood-mediated inflammatory reaction (IBMIR).”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [139]
In the citing paper
“It is thought that a major cause of the initial islet death observed in the immediate aftermath of portal vein islet infusion is due to IBMIR.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [139]
In the citing paper
“Within 15 minutes of contact with host blood, islets are encapsulated within a layer of platelets, reducing nutrient diffusion.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [139]
In the citing paper
“Furthermore, leukocytes infiltrate the islets within an hour, leading to cell death.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [139]
In the citing paper
“Because conventional islet transplantation by infusion into the hepatic portal vein suffers from certain limitations, such as acute graft loss triggered by an instant blood-mediated inflammatory response (IBMIR)”
From Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient. (2024) · cites this paper as [24]
Citations
Cites
No references could be resolved yet.
Research works printed but not linked: 30
- Peppelenbosch, 2001, Cell biology of tissue factor, an unusual member of the cytokine receptor family, Trends Cardiovasc Med, 11, 335, 10.1016/S1050-1738(01)00137-2 · DOI
- Drake, 1989, Selective cellular expression of tissue factor in human tissues: implications for disorders of hemostasis and thrombosis, Am J Pathol, 134, 1087
- Luther, 1996, Tissue factor expression during human and mouse development, Am J Pathol, 149, 101
- Morrissey, 2001, Tissue factor: an enzyme cofactor and a true receptor, Thromb Haemost, 86, 66, 10.1055/s-0037-1616202 · DOI
- Shapiro, 2000, Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen, N Engl J Med, 343, 230, 10.1056/NEJM200007273430401 · DOI · Paper page
- Ryan, 2001, Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol, Diabetes, 50, 710, 10.2337/diabetes.50.4.710 · DOI
- Froberg, 1997, Fatal disseminated intravascular coagulation after autologous islet transplantation, Hum Pathol, 28, 1295, 10.1016/S0046-8177(97)90204-5 · DOI
- Shapiro, 1995, Portal vein thrombosis after transplantation of partially purified pancreatic islets in a combined human liver/islet allograft, Transplantation, 59, 1060, 10.1097/00007890-199504150-00027 · DOI
- Bennet, 1999, Incompatibility between human blood and isolated islets of Langerhans: a finding with implications for clinical intraportal islet transplantation?, Diabetes, 48, 1907, 10.2337/diabetes.48.10.1907 · DOI · Paper page
- Ozmen, 2002, Inhibition of thrombin abrogates the instant blood-mediated inflammatory reaction triggered by isolated human islets: possible application of the thrombin inhibitor melagatran in clinical islet transplantation, Diabetes, 51, 1779, 10.2337/diabetes.51.6.1779 · DOI
- Brandhorst, 1998, Assessment of intracellular insulin content during all steps of human islet isolation procedure, Cell Transplant, 7, 489, 10.1177/096368979800700508 · DOI
- Ricordi, 1988, Automated method for isolation of human pancreatic islets, Diabetes, 37, 413, 10.2337/diab.37.4.413 · DOI
- Lakey, 1999, Intraductal collagenase delivery into the human pancreas using syringe loading or controlled perfusion, Cell Transplant, 8, 285, 10.1177/096368979900800309 · DOI
- Wildgoose, 1990, Synthesis, purification, and characterization of an Argl 52-Glu site-directed mutant of recombinant human blood clotting factor VII, Biochemistry, 29, 3413, 10.1021/bi00465a039 · DOI
- Ekdahl, 1997, Increased phosphate content in complement component C3, fibrinogen, vitronectin, and other plasma proteins in systemic lupus erythematosus: covariation with platelet activation and possible association with thrombosis, Arthritis Rheum, 40, 2178, 10.1002/art.1780401212 · DOI
- Lukinius, 1992, Ultrastructural studies of the ontogeny of fetal human and porcine endocrine pancreas, with special reference to colocalization of the four major islet hormones, Dev Biol, 153, 376, 10.1016/0012-1606(92)90122-W · DOI
- Lukinius, 2001, The transplanted fetal endocrine pancreas undergoes an inherent sequential differentiation similar to that in the native pancreas: an ultrastructural study in the pig-to-mouse model, Diabetes, 50, 962, 10.2337/diabetes.50.5.962 · DOI
- Gong, 1996, Tubing loops as a model for cardiopulmonary bypass circuits: both the biomaterial and the blood-gas phase interfaces induce complement activation in an in vitro model, J Clin Immunol, 16, 222, 10.1007/BF01541228 · DOI
- Larsson, 1997, Inhibition of complement activation by soluble recombinant CR1 under conditions resembling those in a cardiopulmonary circuit: reduced upregulation of CD 1 Ib and complete abrogation of binding of PMNs to the biomaterial surface, Immunopharmacology, 38, 119, 10.1016/S0162-3109(97)00064-7 · DOI
- Parker, 1957, Altered cell strains in continuous culture: a general survey, N YAcad Sci, 5, 303
- Sanchez, 1998, Studies of adsorption, activation, and inhibition of factor XII on immobilized heparin, Tliromb Res, 89, 41, 10.1016/S0049-3848(97)00310-1 · DOI
- Mollnes, 1985, Monoclonal antibodies recognizing a neoantigen of poly(C9) detect the human terminal complement complex in tissue and plasma, Scand J Immunol, 22, 183, 10.1111/j.1365-3083.1985.tb01870.x · DOI
- Nilsson Ekdahl, 1992, Generation of iC3 at the interface between blood and gas, Scand J Immunol, 35, 85, 10.1111/j.1365-3083.1992.tb02837.x · DOI
- Gough, 1988, Rapid and quantitative preparation of cytoplasmic RNA from small numbers of cells, Anal Biochem, 173, 93, 10.1016/0003-2697(88)90164-9 · DOI
- Potgens, 1994, Measurement of tissue factor messenger RNA levels in human endothelial cells by a quantitative RT-PCR assay, Thromb Haemost, 71, 208
- van Suylichem, 1995, Amount and distribution of collagen in pancreatic tissue of different species in the perspective of islet isolation procedures, Cell Transplant, 4, 609, 10.1177/096368979500400610 · DOI
- Colman, 1996, When and where is factor XI activated by thrombin?, Blood, 87, 2089, 10.1182/blood.V87.5.2089.2089 · DOI
- Mavrommatis, 2000, Coagulation system and platelets are fully activated in uncomplicated sepsis, Grit Care Med, 28, 451, 10.1097/00003246-200002000-00027 · DOI
- Pazzagli, 1999, Value of thrombin-antithrombin III complexes in major orthopedic surgery: relation to the onset of venous thromboembolism, Clin Appl Thromb Hemost, 5, 228, 10.1177/107602969900500404 · DOI
- Zhang, 1994, Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice, J Clin Invest, 94, 1320, 10.1172/JCI117451 · DOI
Cited by
Sorted by citations
Items 101–200 of 503
Regenerative medicine and cell-based approaches to restore pancreatic function
Ellis, C. E., Ramzy, A., & Kieffer, T. J. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.93 · Cited by 92
Improved Human Islet Isolation Using Nicotinamide
Ichii, H., Wang, X., Messinger, S., Alvarez, A., Fraker, C., Khan, A., Kuroda, Y., Inverardi, L., Goss, J. A., Alejandro, R., et al. (2006) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2006.01452.x · Cited by 77
“Furthermore, it has been recently reported that islets express and synthesize tissue factor (TF), which triggers a detrimental thrombotic reaction after hepatic portal islet infusion (15,16).”
BackgroundMethodLow Revascularization of Human Islets When Experimentally Transplanted Into the Liver
Lau, J., & Carlsson, P. (2009) · Transplantation · doi:10.1097/tp.0b013e3181943b3d · Cited by 72
“Only in recent years, clinical transplantation of islets to the liver has been seriously questioned based on studies showing both extensive early islet cell death (2) and especially long-term islet graft failure after clinical intraportal transplantation (3).”
BackgroundBerman, D., Cabrera, O., Kenyon, N., Miller, J., Tam, S., Khandekar, V., Picha, K. M., Soderman, A., Jordan, R., Bugelski, P., et al. (2007) · Transplantation · doi:10.1097/01.tp.0000275401.80187.1e · Cited by 76
“15 min), reaching baseline levels 1 day after transplant (9, 20).”
BackgroundCoagulation, Platelets, and Acute Pancreatitis
Kakafika, A., Papadopoulos, V., Mimidis, K., & Mikhailidis, D. (2007) · Pancreas · doi:10.1097/01.mpa.0000240617.66215.d2 · Cited by 76
“Moreover, tifacogin (recombinant TFPI), which was suggested to be beneficial in treating patients with sepsis and low international normalized ratio, might prove useful in controlling the rapid extrapancreatic tissue damage associated with acute pancreatitis.(66,84) Finally, resveratrol has been shown to inhibit the i…”
BackgroundResultCurrent status of clinical islet transplantation.
Korsgren, O., Nilsson, B., Berne, C., Felldin, M., Foss, A., Källén, R., Lundgren, T., Salmela, K., Tibell, A., & Tufveson, G. (2005) · Transplantation · doi:10.1097/01.tp.0000157273.60147.7c · Cited by 76
“We have found and reported considerable variation in the amount of TF expression in islets obtained from different donors (17), and this suggests that expression may be induced.”
BackgroundSelf-citationBrady, A., Martino, M. M., Pedraza, E., Sukert, S., Pileggi, A., Ricordi, C., Hubbell, J. A., & Stabler, C. L. (2013) · Tissue Engineering Part A · doi:10.1089/ten.tea.2012.0686 · Cited by 80
“4 7 As such, there are efforts to develop an alternative site for islet cell transplantation that would minimize exposure of islets to these detrimental conditions.”
Anti-Inflammatory Strategies to Enhance Islet Engraftment and Survival
Citro, A., Cantarelli, E., & Piemonti, L. (2013) · Current Diabetes Reports · doi:10.1007/s11892-013-0401-0 · Cited by 74
“IBMIR is a thrombotic reaction occurring when islets are incubated in ABO-compatible blood, mainly triggered by production and secretion of tissue factor (TF) in islet preparations [2].”
BackgroundEffects of hyperglycemia and hyperinsulinemia on the tissue factor pathway of blood coagulation
Boden, G., & Rao, A. (2007) · Current Diabetes Reports · doi:10.1007/s11892-007-0035-1 · Cited by 74
“It was recently discovered that TF is synthesized in the islets of Langerhans where it has been identified in B -cell granules of C cells [26, 27 ].”
BackgroundTeramura, Y., Oommen, O., Olerud, J., Hilborn, J., & Nilsson, B. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.01.015 · Cited by 73
“, the IBMIR) occurs during the transplantation of cells, such as islets [5,8], mesenchymal stem/stromal cells (MSC) [43], and hepatocytes [44].”
BackgroundSelf-citationTissue Factor-Dependent Procoagulant Activity of Isolated Human Hepatocytes
Stéphenne, X., Vosters, O., Najimi, M., Beuneu, C., Khuu, D. N., Wijns, W., Goldman, M., & Sokal, E. M. (2007) · Liver Transplantation · doi:10.1002/lt.21128 · Cited by 78
“This may compromise the outcome of islet transplantation by early graft loss.(9,10) Therefore, the first aim of this study was to determine if isolated hepatocytes, fresh or cryopreserved, also express TF.”
BackgroundMethodDamodaran, R. G., & Vermette, P. (2018) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.2655 · Cited by 78
“2018;12:1230–1237.y.com/journal/term van Schilfgaarde, 2004; Moberg et al., 2002; Ryan et al., 2002; Thomas et al., 1999).”
Johansson, U., Elgue, G., Nilsson, B., & Korsgren, O. (2005) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2005.01076.x · Cited by 72
“Key words: Endothelial cells, human, islets of Langerhans Abbreviations: AEC, 3-amino, 9-ethyl-carbazole; C3a, Complement3a; CD, cluster of diffrentiation; EC, endothelial cells; ELISA, enzyme-linked immunosorbent assay; HAEC, human aortic endothelial cells; IBMIR, instant blood-mediated inflammatory reaction; IDDM, i…”
BackgroundMethodInfluentialSelf-citationPotential role of mesenchymal stromal cells in pancreatic islet transplantation
Hematti, P., Kim, J., Stein, A. P., & Kaufman, D. B. (2013) · Transplantation Reviews · doi:10.1016/j.trre.2012.11.003 · Cited by 73
“One possible explanation for the decline in graft function over time was a bloodmediated inflammatory reaction during engraftment which leads to reduced islet survival [19].”
BackgroundChen, H., Teramura, Y., & Iwata, H. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.11.011 · Cited by 69
Transplantation for the treatment of type 1 diabetes
Meloche, R. M. (2007) · World Journal of Gastroenterology · doi:10.3748/wjg.13.6347 · Cited by 67
“response that has been shown to lead to islet damage [ 58-60 ]”
BackgroundSvensson, J., Lau, J., Sandberg, M., & Carlsson, P. (2010) · Cell Transplantation · doi:10.3727/096368910x536527 · Cited by 66
“A difference between the two modes of transplantation is that whole-pancreas transplants blood interactions (18), innate immunity (8), and hypoxic events (10).”
BackgroundHogan, A. R. (2007) · Frontiers in bioscience · doi:10.2741/2755 · Cited by 68
“1196 interaction) (149, 150) and after embolization into the liver microenvironment (151), along with the lack of vascularization (and therefore of oxygenation) may contribute to the early functional impairment and loss of islet cell mass (152).”
BackgroundTeramura, Y., & Iwata, H. (2011) · Transplantation · doi:10.1097/tp.0b013e3182034fa4 · Cited by 67
Noguchi, H., Nakai, Y., Ueda, M., Masui, Y., Futaki, S., Kobayashi, N., Hayashi, S., & Matsumoto, S. (2007) · Diabetologia · doi:10.1007/s00125-006-0563-2 · Cited by 67
“However, instant coagulation/inflammation reaction (IBMIR), which is characterised by activation of the coagulation and complement systems, rapid binding and activation of platelets, leucocyte infiltration into the islets [13, 14], and activation of endothelial cells, occurs regularly during this procedure, even witho…”
BackgroundThe transgenic expression of human CD39 on murine islets inhibits clotting of human blood.
Dwyer, K., Mysore, T., Crikis, S., Robson, S., Nandurkar, H., Cowan, P., & d'Apice, A. (2006) · Transplantation · doi:10.1097/01.tp.0000229023.38873.c0 · Cited by 67
“This process is probably triggered by tissue factor expressed on the islets (2) which generates thrombin and subsequently activates platelets.”
BackgroundCurrent state and future evolution of pancreatic islet transplantation
Anazawa, T., Okajima, H., Masui, T., & Üemoto, S. (2018) · Annals of Gastroenterological Surgery · doi:10.1002/ags3.12214 · Cited by 76
Markedly Decreased Blood Perfusion of Pancreatic Islets Transplanted Intraportally Into the Liver
Henriksnäs, J., Lau, J., Zang, G., Berggren, P., Köhler, M. G., & Carlsson, P. (2012) · Diabetes · doi:10.2337/db10-0895 · Cited by 65
“Several factors may contribute to the decline in islet graft function, including implantation of a suboptimal islet mass due to instant cell death (4), lipotoxicity (5), and insufficient vascular engraftment (6) and amyloid deposition (7).”
BackgroundBertuzzi, F., Marzorati, S., Maffi, P., Piemonti, L., Melzi, R., de Taddeo, F., Valtolina, V., D'Angelo, A., di Carlo, V., Bonifacio, E., et al. (2004) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2004-0659 · Cited by 66
“Islets were recently shown to produce and release tissue factor (TF), and it was suggested that this could activate the coagulatory cascade in islet recipients (8).”
BackgroundEffects of Freeze–Thawing and Intravenous Infusion on Mesenchymal Stromal Cell Gene Expression
Hoogduijn, M., de Witte, S. D., Luk, F., Vroonhoven, M. C. G. N. V. D. H.-V., Ignatowicz, L., Catar, R., Strini, T., Korevaar, S., van Ijcken, W. V., Betjes, M., et al. (2016) · Stem Cells and Development · doi:10.1089/scd.2015.0329 · Cited by 65
“It has previously been demonstrated that islets of Langerhans [16], but also culture expanded MSC, can induce IBMIR [2].”
van der Windt, D. J., Marigliano, M., He, J., Votyakova, T., Echeverri, G., Ekser, B., Ayares, D., Lakkis, F., Cooper, D. K. C., Trucco, M., et al. (2012) · Cell Transplantation · doi:10.3727/096368912x653011 · Cited by 65
Huang, X., Moore, D. J., Ketchum, R. J., Nunemaker, C. S., Kovatchev, B. P., McCall, A. L., & Brayman, K. L. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0006 · Cited by 62
“These molecules function in coagulation and are normally expressed at the cell surface of islet -cells and -cells (52).”
BackgroundSu, D., Zhang, N., He, J., Qu, S., Slusher, S., Bottino, R., Bertera, S., Bromberg, J. S., & Dong, H. H. (2007) · Diabetes · doi:10.2337/db07-0371 · Cited by 61
“This deficiency in islet engraftment appears to ensue in syngeneic and immune-deficient hosts, which is indicative of nonimmune-mediated insults to transplanted islets, such as prolonged hypoxia (7; 8; 12; 56) or instant bloodmediated inflammatory reaction (IBMIR) (57-59).”
Reversal of diabetes in pancreatectomized pigs after transplantation of neonatal porcine islets.
Kin, T., Korbutt, G., Kobayashi, T., Dufour, J., & Rajotte, R. (2005) · Diabetes · doi:10.2337/diabetes.54.4.1032 · Cited by 65
Changes in liver enzymes after clinical islet transplantation1
Rafael, E., Ryan, E., Paty, B., Oberholzer, J., Imes, S., Senior, P., McDonald, C., Lakey, J., & Shapiro, A. M. J. (2003) · Transplantation · doi:10.1097/01.tp.0000098822.85924.4c · Cited by 62
Nilsson, P., Ekdahl, K., Magnusson, P., Qu, H., Iwata, H., Ricklin, D., Hong, J., Lambris, J. D., Nilsson, B., & Teramura, Y. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.10.040 · Cited by 60
“This reaction consists of an innate immune attack triggered by activation of the complement and coagulation systems, followed by rapid binding of activated platelets and infiltration of polymorphonuclear leukocytes (PMNs) [3,4].”
Self-citationPrediction of Clinical Outcome in Islet Allotransplantation
Bertuzzi, F., & Ricordi, C. (2007) · Diabetes Care · doi:10.2337/dc06-1233 · Cited by 58
“a coagulation cascade in recipients (72)”
XIAP Overexpression in Islet β‐Cells Enhances Engraftment and Minimizes Hypoxia–Reperfusion Injury
Emamaullee, J., Liston, P., Korneluk, R., Shapiro, A. M. J., & Elliott, J. (2005) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2005.00891.x · Cited by 59
“A substantial portion of the transplanted tissue becomes nonfunctional very soon after injection for a number of causes, including immune response to tissue factor expression in islets and hypoxia-induced damage leading to islet apoptosis (3,4).”
BackgroundPreclinical safety testing of biotechnology-derived pharmaceuticals
Brennan, F., Shaw, L., Wing, M., & Robinson, C. (2004) · Molecular Biotechnology · doi:10.1385/mb:27:1:59 · Cited by 58
“... preventive purposes and include implantation of adenosine deaminase gene-corrected bone marrow stem cells for the treatment of SCID-X1 (51), implantation of cells as a source of an enzyme or cytokine (52), infusion of activated lymphocytes to treat cancer (53), infusion of activated or virus-transfected dendritic…”
BackgroundTransplantation sites for human and murine islets
Stokes, R., Cheng, K., Lalwani, A., Swarbrick, M. M., Thomas, H. E., Loudovaris, T., Kay, T., Hawthorne, W. J., O’Connell, P. J., & Gunton, J. E. (2017) · Diabetologia · doi:10.1007/s00125-017-4362-8 · Cited by 68
“Furthermore, the liver can be a pro-thrombotic and pro-inflammatory environment [15, 16, 39].”
BackgroundMarzorati, S., Antonioli, B., Nano, R., Maffi, P., Piemonti, L., Giliola, C., Secchi, A., Lakey, J., & Bertuzzi, F. (2006) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2006.01512.x · Cited by 57
“This molecule elicits a clotting reaction that triggered an instant bloodmediated inflammatory reaction (IBMIR) during islet infusion into the portal vein (3).”
BackgroundCaiazzo, R. J., Gmyr, V., Hübert, T., Delalleau, N., Lamberts, R., Moerman, E., Kerr-Conte, J. A., & Pattou, F. N. (2007) · Transplantation Proceedings · doi:10.1016/j.transproceed.2007.08.015 · Cited by 52
Adult porcine islets produce MCP‐1 and recruit human monocytes in vitro
Ehrnfelt, C., Kumagai-Braesch, M., Uzunel, M., & Holgersson, J. (2004) · Xenotransplantation · doi:10.1046/j.1399-3089.2003.00104.x · Cited by 56
“MCP-1 has also been reported to induce expression of tissue factor in human monocytes; tissue factor may initiate coagulation and subsequent destruction of transplanted islets undergoing IBMIR [21,22].”
BackgroundInfluentialBisphenol A enhances kisspeptin neurons in anteroventral periventricular nucleus of female mice
Wang, X., Chang, F., Bai, Y., Chen, F., Zhang, J., & Chen, L. (2014) · Journal of Endocrinology · doi:10.1530/joe-13-0475 · Cited by 58
Bivalirudin in Combination with Heparin to Control Mesenchymal Cell Procoagulant Activity
Stephenne, X., Nicastro, E., Eeckhoudt, S., Hermans, C., Nyabi, O., Lombard, C., Najimi, M., & Sokal, E. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042819 · Cited by 54
Tokodai, K., Goto, M., Inagaki, A., Nakanishi, W., Ogawa, N., Satoh, K., Kawagishi, N., Sekiguchi, S., Nilsson, B., Okada, N., et al. (2010) · Transplantation · doi:10.1097/tp.0b013e3181ffb9f5 · Cited by 54
“The finding that TF is expressed not only on the islet grafts (4) but also on the activated leukocytes in the hosts after islet transplantation indicates to us the possibility that TF, induced on the recipient granulocytes, could be a novel target to inhibit the IBMIR.”
BackgroundSelf-citationJung, Y. S., Jeong, J., Yook, S., Im, B.-H., Seo, J., Hong, S. W., Park, J., Yang, V. C.-M., Lee, D. Y., & Byun, Y. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.09.051 · Cited by 57
Toward Engineering a Novel Transplantation Site for Human Pancreatic Islets
Smink, A. M., Faas, M. M., & de Vos, P. (2013) · Diabetes · doi:10.2337/db12-1553 · Cited by 53
Lund, T., Fosby, B., Korsgren, O., Scholz, H., & Foss, A. E. (2008) · Transplant International · doi:10.1111/j.1432-2277.2008.00664.x · Cited by 47
Self-citationPharoun, J., Berro, J., Sobh, J., Abou-Younes, M.-M., Nasr, L., Majed, A., Khalil, A., Joseph, J., Stephan, & Faour, W. H. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176719 · Cited by 55
The Interface Between Coagulation and Immunity
Shrivastava, S., McVey, J. H., & Dorling, A. (2007) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2006.01653.x · Cited by 51
“It occurs because islets express TF (58) and it is likely that this IBMIR partly explains the necessity for multiple transplants and it almost certainly contributes to the acute portal vein thrombosis reported after islet infusion.”
BackgroundMicrofluidic-Based Droplets for Advanced Regenerative Medicine: Current Challenges and Future Trends
Nazari, H., Heirani‐Tabasi, A., Ghorbani, S., Eyni, H., Bazaz, S. R., Khayati, M., Gheidari, F., Moradpour, K., Kehtari, M., Tafti, S. M. A., et al. (2021) · Biosensors · doi:10.3390/bios12010020 · Cited by 61
“Droplet-based encapsulation methods can increase the safety of the encapsulation process, control the size of scaffolds, permit long-term culture periods, and prepare immunological protection of these pancreatic islets in the engineering of pancreatic tissue [109].”
BackgroundWang, X., Wang, K., Zhang, W., Ming, Q., & Luo, Y. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.05.033 · Cited by 54
Ji, M., Yi, S., Smith-Hurst, H., Phillips, P., Wu, J.-J., Hawthorne, W., & O'Connell, P. (2011) · Transplantation · doi:10.1097/tp.0b013e3182106091 · Cited by 49
“Blocking TF using an inhibitory monoclonal antibody prevents the response in vitro (10).”
BackgroundMethodInfluentialDuprez, I., Johansson, U., Nilsson, B., Korsgren, O., & Magnusson, P. (2011) · Upsala Journal of Medical Sciences · doi:10.3109/03009734.2010.524320 · Cited by 49
Self-citationCurrent status of islet cell transplantation
Ichii, H., & Ricordi, C. (2008) · Journal of Hepato-Biliary-Pancreatic Surgery · doi:10.1007/s00534-008-0021-2 · Cited by 102
“Since the success of the Edmonton protocol, heparin has been added in order to reduce the clotting process, termed the instant blood mediated inflammatory reaction (IBMIR), occurring in the islet infusion site [63, 64].”
Dyachok, O., Tufveson, G., & Gylfe, E. (2004) · Cell Calcium · doi:10.1016/j.ceca.2003.11.004 · Cited by 49
Self-citationKawahara, T., Kin, T., & Shapiro, A. M. J. (2011) · Journal of Hepato-Biliary-Pancreatic Sciences · doi:10.1007/s00534-011-0441-2 · Cited by 52
“Blockage of the blood flow either due to portal vein thrombosis or transplanted islet emboli induces a local inflammatory reaction called an immediate blood-mediated inflammatory reaction (IBMIR), resulting in functional loss of islet grafts following intraportal islet transplantation, and this could increase the risk…”
BackgroundInfluentialBerney, T., & Toso, C. (2006) · Diabetes & Metabolism · doi:10.1016/s1262-3636(06)72803-8 · Cited by 47
Egami, M., Haraguchi, Y., Shimizu, T., Yamato, M., & Okano, T. (2013) · Archives of pharmacal research · doi:10.1007/s12272-013-0299-8 · Cited by 47
“To resolve these problems, tissue engineered methodology have been progressing rapidly as the second generation cell-based regenerative therapy, and the various clinical studies have already started (Langer and Vacanti 1993; Li et al. 1999; Ochi et al. 2002; Wakitani et al. 2002; Moberg et al. 2002; Atala et al. 2006,…”
Thrombomodulin Improves Early Outcomes After Intraportal Islet Transplantation
Cui, W., Wilson, J. T., Wen, J., Angsana, J., Qu, Z., Haller, C., & Chaikof, E. (2009) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2009.02652.x · Cited by 47
“amine the effects of TM vesicle formulations (9,10).”
BackgroundAllogeneic islet transplantation
Marzorati, S., Pileggi, A., & Ricordi, C. (2007) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.7.11.1627 · Cited by 46
“Islet cells actively contribute to this phenomenon by producing tissue factor [169] , monocyte chemoattractant protein-1 [170-172] and CD154 [173,174] amongst other proinflammatory molecules [175] that may have an impact on graft outcome.”
BackgroundRequirements for success in clinical islet transplantation.
Ricordi, C., Inverardi, L., Kenyon, N., Goss, J., Bertuzzi, F., & Alejandro, R. (2005) · Transplantation · doi:10.1097/01.tp.0000157275.64874.84 · Cited by 47
Human Pancreatic Duct Cells Exert Tissue Factor-Dependent Procoagulant Activity
Beuneu, C., Vosters, O., Movahedi, B., Remmelink, M., Salmon, I. J., PIPELEERS, D. G., Pradier, O., Goldman, M., & Verhasselt, V. (2004) · Diabetes · doi:10.2337/diabetes.53.6.1407 · Cited by 45
“In the context of islet transplantation, the so-called instant blood-mediated inflammatory reaction likely contributes to early -cell loss (5).”
BackgroundMethodInfluentialTotal Pancreatectomy with Islet Autologous Transplantation: The Cure for Chronic Pancreatitis?
Kesseli, S., Smith, K. A., & Gardner, T. (2015) · Clinical and Translational Gastroenterology · doi:10.1038/ctg.2015.2 · Cited by 46
“It is believed that intraportal micro-thrombosis or transient ischemia following islet infusion may contribute significantly to graft loss due to the secretion of tissue factor by the islet cells in response to the clotting reaction.(52) This process has been termed instant blood mediated inflammatory injury, and has…”
BackgroundTreating diabetes with islet transplantation: Lessons from the past decade in Lille
Vantyghem, M., Defrance, F., Quintin, D., Leroy, C., Raverdi, V., Prévost, G., Caiazzo, R. J., Kerr-Conte, J. A., Glowacki, F., Hazzan, M., et al. (2014) · Diabetes & Metabolism · doi:10.1016/j.diabet.2013.10.003 · Cited by 54
“These events drive the expression of inflammatory genes such as the tissue factor (TF) and monocyte chemotactic protein-1 (MCP-1) genes [39].”
BackgroundGoto, M., Groth, C., Nilsson, B., & Korsgren, O. (2004) · Xenotransplantation · doi:10.1046/j.1399-3089.2003.00107.x · Cited by 46
“However, we have previously described that both pig [2, 17] and human islets [4, 6] induce a strong innate immune response when in contact with human blood.”
BackgroundSelf-citationIslet Transplantation in Patients with Diabetes Mellitus
Nanji, S. A., & Shapiro, A. M. J. (2004) · BioDrugs · doi:10.2165/00063030-200418050-00004 · Cited by 71
Lee, C., Dhawan, A., Smith, R., Mitry, R., & Fitzpatrick, E. (2016) · Cell Transplantation · doi:10.3727/096368916x691286 · Cited by 45
Biomolecular Surface Engineering of Pancreatic Islets with Thrombomodulin
Wilson, J. T., Haller, C., Qu, Z., Cui, W., Urlam, M. K., & Chaikof, E. (2010) · Acta Biomaterialia · doi:10.1016/j.actbio.2010.01.027 · Cited by 45
“While a direct comparison with soluble heparin was not made, in light of the inefficacy of systemically administered heparin during clinical islet transplantation [2,20,21], these findings potentially illustrate the increased therapeutic benefit achieved through local delivery of anticoagulants to the portal bed.”
BackgroundHaque, M. R., Kim, J., Park, H., Lee, H. S., Lee, K. W., Al-Hilal, T. A., Jeong, J., Ahn, C., Lee, D. S., Kim, S. J., et al. (2017) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.04.021 · Cited by 41
“Tissue factors are the primary regulator of blood coagulation cascade, which is expressed by and released from β and α cells of islets [74,75].”
BackgroundIslet surface modification with urokinase through DNA hybridization.
Takemoto, N., Teramura, Y., & Iwata, H. (2011) · Bioconjugate chemistry · doi:10.1021/bc100453r · Cited by 44
Immunological aspects of pancreatic islet cell transplantation
Azzi, J., Geara, A., El-Sayegh, S., & Abdi, R. (2010) · Expert Review of Clinical Immunology · doi:10.1586/eci.09.67 · Cited by 44
Ekdahl, K., Hong, J., Hamad, O., Larsson, R., & Nilsson, B. (2013) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4614-4118-2_18 · Cited by 44
Self-citationPancreatic Islet Cell Transplantation: An Update for Interventional Radiologists
Gaba, R. C., Garcı́a-Roca, R., & Oberholzer, J. (2012) · Journal of Vascular and Interventional Radiology · doi:10.1016/j.jvir.2012.01.057 · Cited by 43
“As transplanted islets can activate coagulation by ecreting tissue factor (83) and may cause portal flow reducion, stagnation, and clot formation through embolic effects, ntraprocedural systemic anticoagulation and portal venous ressure monitoring are necessary.”
BackgroundInfluence of microenvironment on engraftment of transplanted β-cells
Carlsson, P. (2011) · Upsala Journal of Medical Sciences · doi:10.3109/03009734.2010.548609 · Cited by 40
“This so-called IBMIR occurs in clinical islet transplantation as shown by an increase in concentrations of thrombin–antithrombin complex immediately after islet infusion, and the parallel increase in c-peptide release indicates massive bcell death (7).”
Overcoming the Challenges Now Limiting Islet Transplantation
Pileggi, A., Cobianchi, L., Inverardi, L., & Ricordi, C. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1375.059 · Cited by 58
Zhu, H.-Q., Wang, J.-Z., Jiang, H.-C., Ma, Y., Pan, S.-H., Reddy, S., & Sun, X.-Y. (2010) · Experimental and Molecular Medicine · doi:10.3858/emm.2010.42.11.075 · Cited by 42
“Recent evidence indicates that IBMIR may be triggered, in large part, by islets in direct contact with blood (Moberg et al., 2002; Johansson et al., 2005; Moberg, 2005).”
BackgroundProlactin Supplementation to Culture Medium Improves β-Cell Survival
Yamamoto, T., Mita, A., Ricordi, C., Messinger, S., Miki, A., Sakuma, Y., Timoneri, F., Barker, S., Fornoni, A., Molano, R. D., et al. (2010) · Transplantation · doi:10.1097/tp.0b013e3181d98af1 · Cited by 41
“Those proinflammatory mediators have been negatively associated with clinical islet transplant outcomes (41, 42).”
BackgroundSaito, Y., Goto, M., Maya, K., Ogawa, N., Fujimori, K., Kurokawa, Y., & Satomi, S. (2010) · Cell Transplantation · doi:10.3727/096368910x508889 · Cited by 42
Lim, J., Mitroulis, I., Ferreira, A. V., Chen, L., Gercken, B., Steffen, A., Kemter, E., Ameln, A. K., Waskow, C., Hosur, K. B., et al. (2015) · Thrombosis and Haemostasis · doi:10.1160/th15-05-0429 · Cited by 48
Chhabra, P., Wang, K.-J., Zeng, Q., Jecmenica, M., Langman, L., Linden, J., Ketchum, R., & Brayman, K. (2010) · Cell Transplantation · doi:10.3727/096368910x491806 · Cited by 41
Jacobs‐Tulleneers‐Thevissen, D., Bartholomeus, K., Suenens, K. G., Vermeulen, I., Ling, Z., Hellemans, K., Veld, P. I. '., Pipeleers‐Marichal, M., & PIPELEERS, D. G. (2010) · Diabetologia · doi:10.1007/s00125-010-1721-0 · Cited by 43
“[33] our human islet cell preparations also express tissue factor that can induce blood coagulation in vitro [11]; however, we found it predominantly in the duct cells that are known to be much more abundant in human than in rat islet cell preparations [9, 10].”
BackgroundLiver Cell Transplantation: Basic Investigations for Safe Application in Infants and Small Children
Meyburg, J., Alexandrova, K., Barthold, M., Kafert-Kasting, S., Schneider, A., Attaran, M., Hoerster, F., Schmidt, J., Hoffmann, G., & Ott, M. (2009) · Cell Transplantation · doi:10.3727/096368909x470775 · Cited by 41
“Surprisingly, this was only found in two of the four batches, while the values even increased after an increase in portal venous pressure has been shown in several animal studies of LCT (3,18,22,30) and may fa- cryopreservation in the other two.”
ResultKanak, M. A., Takita, M., Itoh, T., SoRelle, J. A., Murali, S., Kunnathodi, F., Shahbazov, R., Lawrence, M. C., Levy, M. F., & Naziruddin, B. (2014) · Transplantation · doi:10.1097/tp.0000000000000107 · Cited by 42
“Tissue Factor Expression in Islets Islets can express TF, which could potentially trigger coagulation and induce inflammation (8).”
BackgroundKim, J.-S., Lim, J.-H., Nam, H., Lim, H.-J., Shin, J., Shin, J.-Y., Ryu, J.-H., Kim, K., Kwon, I. C., Jin, S., et al. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.07.018 · Cited by 45
Ma, X., Ye, B., Gao, F., Liang, Q., Dong, Q., Liu, Y., Rong, P.-F., Wang, W., & Yi, S. (2012) · Cell Transplantation · doi:10.3727/096368911x580563 · Cited by 40
Large-Scale Comparison of Liberase HI and Collagenase NB1 Utilized for Human Islet Isolation
Brandhorst, H., Friberg, A., Nilsson, B., Andersson, H. H., Felldin, M., Foss, A., Salmela, K., Tibell, A., Tufveson, G., Korsgren, O., et al. (2010) · Cell Transplantation · doi:10.3727/096368909x477507 · Cited by 40
Self-citationCharacterization of pancreatic ductal cells in human islet preparations
Ichii, H., Miki, A., Yamamoto, T., Molano, R. D., Barker, S., Mita, A., Rodriguez‐Diaz, R., Klein, D., Pastori, R. L., Alejandro, R., et al. (2008) · Laboratory Investigation · doi:10.1038/labinvest.2008.87 · Cited by 38
“Moreover, contaminating PDC may contribute to early b-cell damage after intrahepatic islet transplantation through their expression of TF.(19,28,29)”
BackgroundMethodInfluentialCoppens, V., Heremans, Y., Leuckx, G., Suenens, K. G., Jacobs‐Tulleneers‐Thevissen, D., Verdonck, K., Lahoutte, T., Luttun, A., Heimberg, H., & Leu, N. D. (2012) · Diabetologia · doi:10.1007/s00125-012-2754-3 · Cited by 41
“exert a beneficial effect on the deleterious consequences of instant blood-mediated inflammatory reaction, initially described after intra-portal islet transplantation [18] and potentially stimulated by the use of a blood clot in the current model.”
BackgroundPancreatic islet transplantation for treating diabetes
Matsumoto, S., Noguchi, H., Yonekawa, Y., Okitsu, T., Iwanaga, Y., Liu, X., Nagata, H., Kobayashi, N., & Ricordi, C. (2005) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.6.1.23 · Cited by 35
“IBMIR is a thrombotic/inflammatory reaction, which is elicited when islets come in direct contact with ABO-compatible blood [95-97].”
BackgroundMicro-fabricated scaffolds lead to efficient remission of diabetes in mice
Buitinga, M., Assen, F. P., Hanegraaf, M. A. J., Wieringa, P. A., Hilderink, J., Moroni, L., Truckenmüller, R. K., van Blitterswijk, C., Römer, G. R. B. E., Carlotti, F., et al. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.03.031 · Cited by 45
“This has been shown to cause islet destruction and islet loss [3,4].”
Complement inhibition in biomaterial- and biosurface-induced thromboinflammation
Ekdahl, K., Huang, S., Nilsson, B., & Teramura, Y. (2016) · Seminars in Immunology · doi:10.1016/j.smim.2016.04.006 · Cited by 38
“The administration of these cells is usually associated with a large loss of transplanted cells as the result of thromboinflammation [49] [50] [51] 54] , which is also termed the instant blood-mediated inflammatory reaction (IBMIR).”
Self-citationIslet transplantation for Type 1 diabetes: where are we now?
Ahearn, A., Parekh, J. R., & Posselt, A. M. (2014) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.2015.978291 · Cited by 42
“Second, intravenous infusion of the islets exposes them to a severe non-specific inflammatory response called the IBMIR that rapidly destroys much of the islet inoculum [35,36].”
BackgroundSatoh, M., Yasunami, Y., Matsuoka, N., Nakano, M., Itoh, T., Nitta, T., Anzai, K., Ono, J., Taniguchi, M., & Ikeda, S. (2007) · Transplantation · doi:10.1097/01.tp.0000260161.81775.58 · Cited by 38
Immune Protection of Stem Cell-Derived Islet Cell Therapy for Treating Diabetes
Tahbaz, M., & Yoshihara, E. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.716625 · Cited by 43
Im, B.-H., Jeong, J., Haque, M. R., Lee, D. Y., Ahn, C., Kim, J. E., & Byun, Y. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.11.028 · Cited by 41
Cuccuini, W., Poitevin, S., Poitevin, G., Dignat-George, F., Cornillet-Lefebvre, P., Sabatier, F., & Nguyen, P. (2010) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2010.03936.x · Cited by 37
Akima, S., Hawthorne, W. J., Favaloro, E. J., Patel, A. P., Blyth, K. M., Mudaliar, Y., Chapman, J. R., & O’Connell, P. J. (2009) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2009.02673.x · Cited by 38
“However, the success of the procedure is limited by the profound islet attrition that occurs in the immediate posttransplant period, leaving a final islet cell survival of around 20–40% of a healthy nondiabetic subject (3).”
BackgroundInfluentialGaykema, L., van Nieuwland, R. V., Dekkers, M. C., van Essen, M. V., Heidt, S., Zaldumbide, A., van den Berg, C. W., Rabelink, T., & van Kooten, C. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1058763 · Cited by 36
Oxygenation of the Intraportally Transplanted Pancreatic Islet
Suszynski, T. M., Avgoustiniatos, E. S., & Papas, K. K. (2016) · Journal of Diabetes Research · doi:10.1155/2016/7625947 · Cited by 40
Senior, P. A., Kin, T., Shapiro, J., & Koh, A. (2012) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2012.01.002 · Cited by 42
Islet Transplantation: Factors in Short-Term Islet Survival
Deters, N. A., Stokes, R., & Gunton, J. E. (2011) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-011-0143-0 · Cited by 39
“ADSC Adipose derived stem cells IBMIR Instant blood-mediated inflammatory reaction MSC Mesenchymal stem cells SC Sertoli cells T1D Type 1 diabetes”
BackgroundInfluentialWilson, J. T., & Chaikof, E. L. (2008) · Journal of Diabetes Science and Technology · doi:10.1177/193229680800200502 · Cited by 34
Emamaullee, J. A., Pepper, A. R., & Shapiro, A. M. J. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-809880-6.00056-4 · Cited by 12
Metadata
- Authors
- Moberg, L., Johansson, H., Lukinius, A., Berne, C., Foss, A., Källen, R., Østraat, Ø., Salmela, K., Tibell, A., Tufveson, G., Elgue, G., Ekdahl, K. N., Korsgren, O., & Nilsson, B.
- Affiliations
- Uppsala University (SE)
- Uppsala University Hospital (SE)
- University of Helsinki (FI)
- Corresponding author
- Nilsson, B
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2002-12
- Volume
- 360
- Issue
- 9350
- Pages
- 2039-2045
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2158070939
- Cited by
- 568
- References
- 0
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 13 · 2023: 17 · 2022: 16 · 2021: 13 · 2020: 24 · 2019: 37 · 2018: 23 · 2017: 24 · 2016: 35 · 2015: 25 · 2014: 26 · 2013: 29 · 2012: 29
- FWCI
- 16.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Knut och Alice Wallenbergs Stiftelse
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- tissue factor, islet transplantation, type 1 diabetes, coagulation activation, islet damage, factor VIIa, islet endocrine cells, graft loss, insulin secretion
- MeSH terms
- Adult, Blood Cell Count, Diabetes Mellitus, Type 1, Female, Humans, Islets of Langerhans, Male, Middle Aged, Postoperative Complications, Precipitin Tests, Thromboplastin, Thrombosis, Islets of Langerhans Transplantation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
