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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…
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“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]
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“Coagulation and platelet activation triggered by the exposure of hidden surface molecules on islets and antibody-mediated complement activation contribute to the development of IBMIR (11, 16, 17).”
BackgroundActivation and Regulation of Hemostasis in Acute Liver Failure and Acute Pancreatitis
Lisman, T., & Porte, R. (2010) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0030-1254052 · Cited by 35
“In studies of pancreatic islet transplantation it has been demonstrated that endocrine (but not exocrine) cells of the pancreas express tissue factor.(41) In patients with advanced DIC, the disease may eventually be complicated by bleeding as a result of the exhaustion of hemostatic factors or erosion of vessels, and…”
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“All these events are part of the IBMIR reaction, a key component of the early post-transplant loss of islets [26,28-30].”
BackgroundA New Method for Incorporating Functional Heparin onto the Surface of Islets of Langerhans
Cabric, S., Eich, T., Sánchez, J., Nilsson, B., Korsgren, O., & Larsson, R. L. (2008) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2007.0312 · Cited by 34
“IBMIR, elicited by islets of Langerhans at the time of intraportal transplantation, 5,6,8 is one such example that stimulated the development of the new method for applying immobilized heparin onto surfaces of biological origin as described in this paper.”
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“The increase in TAT complex levels was concomitant with an increase in C-peptide, indicating release from damaged islets.(5,6) The ability to monitor function, injury or cell death after islet transplantation is limited, and the search for suitable biomarkers is ongoing.”
Self-citationShielding Engineered Islets With Mesenchymal Stem Cells Enhance Survival Under Hypoxia
Chandravanshi, B., & Bhonde, R. R. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25885 · Cited by 37
“There is an extensive loss of b cell mass (50%) within first few minutes of transplantation due to blood mediated inflammatory reactions leading to endocrine cell damage [Moberg et al., 2002; Eich et al., 2007].”
BackgroundSmink, A. M., de Haan, B. J., Paredes-Juarez, G. A., Wolters, A. H. G., Kuipers, J., Giepmans, B. N. G., Schwab, L. W., Engelse, M. A., van Apeldoorn, A. A., de Koning, E. J. P., et al. (2016) · Biomedical Materials · doi:10.1088/1748-6041/11/3/035006 · Cited by 35
“Moreover, a polymer scaffold could prevent the direct exposure of islets to blood and therefore prevent the enormous islet loss associated with IBMIR [17].”
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Sustained Reversal of Diabetes Following Islet Transplantation to Striated Musculature in the Rat
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“planted islets are destroyed shortly after infusion, due to islet–blood interactions [2, 3, 5–8].”
BackgroundSelf-citationIntrahepatic Islet Transplant in the Mouse: Functional and Morphological Characterization
Melzi, R., Sanvito, F., Mercalli, A., Andralojc, K., Bonifacio, E., & Piemonti, L. (2008) · Cell Transplantation · doi:10.3727/096368908787648146 · Cited by 33
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“A key molecular step in IBMIR is islet expression of tissue factor (TF) (34,35).”
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“Several factors may contribute to islet graft dysfunction at the liver site, which includes early cell death, lipotoxicity, immunological factors, as well as insufficient engraftment (10,14,23,25).”
BackgroundExtracellular Matrix and Growth Factors Improve the Efficacy of Intramuscular Islet Transplantation
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“A majority of intrahepatic transplanted islets fail to engraft for a number of reasons, including instant blood-mediated inflammatory reaction [1], the influence of immunosuppressants [2], and excessive hepatic lipogenesis [3].”
BackgroundDual Islet Transplantation Modeling of the Instant Blood-Mediated Inflammatory Reaction
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“Islets, and not pancreatic exocrine tissue, can express tissue factor, which has been implicated as a stimulus in the initiation of coagulation (41,61,62).”
BackgroundAngaswamy, N., Saini, D., Ramachandran, S., Benshoff, N. D., Liu, W., Chapman, W. C., & Mohanakumar, T. (2009) · Transplantation · doi:10.1097/tp.0b013e3181b9cbc4 · Cited by 38
“Further, instant blood-mediated inflammatory reactions negatively influence islet engraftment and survival (14, 15).”
BackgroundThe instant blood‐mediated inflammatory reaction in xenogeneic islet transplantation
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Self-citationThromboinflammation in Therapeutic Medicine.
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Self-citationNo Time to Die—How Islets Meet Their Demise in Transplantation
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“Approximately 25% of transplanted islets are lost immediately [15] as they come into contact with intraportal ABO-compatible whole blood, triggered by exposed tissue factor on the surface of the islets [16].”
BackgroundFrom Disease and Patient Heterogeneity to Precision Medicine in Type 1 Diabetes
den Hollander, N. H. M., & Roep, B. O. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.932086 · Cited by 33
“Transplant recipients receive immunosuppressants, but these are not sufficient to reverse pre-existent B and T cell autoimmune reactions and often harm beta-cell differentiation and function (89, 96, 97).”
BackgroundCurrent status of porcine islet xenotransplantation
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“5,6 This has led to the search for alternative transplantation sites.”
Fujita, M., McGrath, K. M., Bottino, R., Dons, E. M., Long, C. E., Kumar, G., Ekser, B., Echeverri, G. J., Hata, J., Haruma, K., et al. (2013) · Cell Transplantation · doi:10.3727/096368912x662381 · Cited by 29
“%) through an inflammatory response known as the instant bloodmediated inflammatory reaction (IBMIR) (3,6,21,37).”
BackgroundInfluentialRedox-Dependent Inflammation in Islet Transplantation Rejection
Barra, J. M., & Tse, H. M. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00175 · Cited by 29
Polymeric nano-shielded islets with heparin-polyethylene glycol in a non-human primate model
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HMGB1-Mediated Early Loss of Transplanted Islets Is Prevented by Anti–IL-6R Antibody in Mice
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“Instant blood-mediated immune responses including complement have been reported to play an essential role in the early loss of transplanted islets in the liver.(25,26) However, the mechanistic analysis with respect to simultaneous and/or subsequent in vivo immune responses in the liver, site of islet transplantation,…”
BackgroundBrain Death–Induced Inflammatory Activity in Human Pancreatic Tissue
Rech, T. H., Crispim, D., Rheinheimer, J., Barkan, S. S., Osvaldt, A. B., Filho, T. D. J. M. G., Kruel, C. D. P., Martini, J., Gross, J. L., & Leitão, C. B. (2013) · Transplantation · doi:10.1097/tp.0b013e3182a949fa · Cited by 29
“Infusion of TF-expressing islets into the portal vein triggered an instant blood-mediated inflammatory reaction characterized by rapid binding of platelets to islet surface (24, 25).”
BackgroundKey factors for human islet isolation and clinical transplantation.
Goto, M., Johansson, U., Eich, T., Lundgrem, T., Engkvist, M., Felldin, M., Foss, A., Källén, R., Salmela, K., Tibell, A., et al. (2004) · Transplantation Proceedings · doi:10.1097/00007890-200407271-00949 · Cited by 28
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“The exposure of islets to portal blood triggers an instant bloodmediated inflammatory reaction (IBMIR) that causes the acute destruction of a significant portion of the transplanted islets [28,29].”
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“This is mainly because most of the islets transplanted into the liver via the portal vein are subsequently destroyed after PITx.(1,2) The islet isolation process itself also triggers a cascade of stressful events in the islets involving apoptosis and the production of proinflammatory molecules that negatively influenc…”
BackgroundExpression of Pro- and Antiapoptotic Molecules of the Bcl-2 Family in Human Islets Postisolation
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Immunology of pancreatic islet transplantation
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“Interestingly, human islets express tissue factor (TF), an integral component in the coagulation cascade [13].”
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“Activation of coagulation could be triggered through both the intrinsic pathway by islet surface collagen residues and the extrinsic pathway by tissue factors or monocyte chemoattractive protein-1 (MCP1) [34, 35].”
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“Intrahepatic islet infusion in men is associated with an immediate bloodmediated inflammatory reaction, thrombosis, and hepatic tissue ischemia with elevated blood liver enzymes [34–45].”
BackgroundConsiderations for an Alternative Site of Islet Cell Transplantation
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“Instant blood-mediated inflammatory reaction describes an innate immune response occurring when pancreatic endothelial cells encounter ABO-compatible blood and release tissue factor, activating the coagulation and complement cascades that result in leukocyte and macrophage-mediated islet cell death.(5,6) Some inflamma…”
BackgroundRGD-containing elastin like polypeptide improves islet transplantation outcomes in diabetic mice.
Lee, K.-M., Kim, J.-H., Choi, E.-S., Kim, E., Choi, S.-K., & Jeon, W. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.06.011 · Cited by 25
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“36 mg/kg; red lines) or high ATG doses (H-group [1, 5, 6, 9, 10]; 5.”
BackgroundEffect of nicotinamide on early graft failure following intraportal islet transplantation
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Efficacy of DHMEQ, a NF-κB Inhibitor, in Islet Transplantation
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Imaging the islet graft by positron emission tomography
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“The acute loss of islet function has partly been attributed to a process called the Instant blood-mediated inflammatory reaction (IBMIR) [7–9].”
BackgroundStriated Muscle as Implantation Site for Transplanted Pancreatic Islets
Espes, D., Eriksson, O., Lau, J., & Carlsson, P. (2011) · Journal of Transplantation · doi:10.1155/2011/352043 · Cited by 22
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“The expression of tissue factor by beta cells and by contaminating duct cells has been shown to trigger coagulation events [1, 2].”
BackgroundMethodState of the Art: Islet Transplantation for the Cure of Type 1 Diabetes Mellitus
Hirshberg, B., Rother, K., Digon, B. J. I., Venstrom, J., & Harlan, D. (2003) · Reviews in Endocrine & Metabolic Disorders · doi:10.1023/a:1027358230402 · Cited by 24
“One potential mechanism underlying the near immediate loss of islet function post-infusion is the recently described “instant blood-mediated inflammatory reaction” (IBMIR) [51,70,71].”
BackgroundInfluentialIslet transplantation: immunological perspectives.
Inverardi, L., Kenyon, N., & Ricordi, C. (2003) · Current Opinion in Immunology · doi:10.1016/s0952-7915(03)00115-8 · Cited by 24
“In vitro studies revealed that inhibitors of coagulation, such as inactivated factor VIIa, effectively prevented islet-induced coagulation in allogeneic blood, thereby suggesting that recipient treatment with such inhibitors may aid in the prevention of early islet loss and enable insulin independence with fewer islet…”
BackgroundA brief review of the current status of pig islet xenotransplantation
Cooper, D. K. C., Mou, L., & Bottino, R. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1366530 · Cited by 33
Pancreatic islet transplantation: toward definitive treatment for diabetes mellitus
Takaki, T., & Shimoda, M. (2020) · Global Health & Medicine · doi:10.35772/ghm.2020.01057 · Cited by 33
“(49) determined that tissue factor (TF) from pancreatic islets serves as the main trigger of IBMIR and that the clotting reaction triggered by 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.”
BackgroundYu, C., Juang, J., Lin, Y., Kuo, C., Hsieh, L., & Huang, C. (2020) · Advanced Biosystems · doi:10.1002/adbi.201900254 · Cited by 21
Coppin, L. C. F., Smets, F., Ambroise, J., Sokal, E., & Stephenne, X. (2020) · Stem cell research & therapeutics · doi:10.1186/s13287-020-1572-7 · Cited by 23
Kesseli, S. J., Wagar, M. K., Jung, M. K., Smith, K. D., Lin, Y. K., Walsh, M. R., Hatipoğlu, B., Freeman, M. L., Pruett, T. L., Beilman, G. J., et al. (2017) · The American Journal of Gastroenterology · doi:10.1038/ajg.2017.14 · Cited by 26
“Chronic, n (%) 30 (91) 122 (86) Recurrent acute, n (%) 3 (9) 20 (14) Etiology of pancreatitis Hereditary, n (%) 8 (24) 26 (19) 0.”
Porcine Islet Xenografts: a Clinical Source of ß-Cell Grafts
Salama, B. F., & Korbutt, G. S. (2017) · Current Diabetes Reports · doi:10.1007/s11892-017-0846-7 · Cited by 25
Current Concepts of Using Pigs as a Source for Beta-Cell Replacement Therapy of Type 1 Diabetes
Klymiuk, N., Ludwig, B., Seissler, J., Reichart, B., & Wolf, E. (2016) · Current Molecular Biology Reports · doi:10.1007/s40610-016-0039-1 · Cited by 23
Oura, T., Ko, D. S. C., Boskovic, S., O’Neil, J. J., Chipashvili, V., Koulmanda, M., Hotta, K., Kawai, K., Nadazdin, O., Smith, R. N., et al. (2016) · Cell Transplantation · doi:10.3727/096368915x688966 · Cited by 26
“3, marked with X), which may indicate some islets of these recipients were destroyed by an instant blood-mediated inflammatory reaction (IBMIR) (16,25).”
BackgroundNeonatal Sepsis in the Very Low Birth Weight Preterm Infants: Part 1: Review of Patho-physiology
Haque, K. N. (2010) · doi:10.2174/1996327001003010001 · Cited by 13
Darwish, M. A., Abdelbakky, M., Messiha, B., Abo-Saif, A., & Abo-Youssef, A. M. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174059 · Cited by 22
Liljebäck, H., Grapensparr, L., Olerud, J., & Carlsson, P. (2016) · Cell Transplantation · doi:10.3727/096368915x688902 · Cited by 22
“Occurrence of an immediate blood-mediated inflammatory reaction when exposing islets to portal blood has been shown to damage the endocrine cells (20) and cause a loss of islet mass up to 50% within the first minutes posttransplantation (11).”
BackgroundPileggi, A., Fenjves, E., Klein, D., Ricordi, C., & Pastori, R. (2004) · IUBMB Life · doi:10.1080/15216540400006469 · Cited by 22
“A wide array of proinflammatory molecules is expressed by pancreatic islets b -cells ( 21 ), including cytokine receptors ( 19 ), CD14 (endotoxin receptor) and Toll-like receptors ( 18 ), monocyte chemoattractant protein-1 (MCP-1) ( 22 ), and tissue factor ( 23 ).”
BackgroundNanotechnology Approaches to Modulate Immune Responses to Cell-based Therapies for Type 1 Diabetes
Wiggins, S., Abuid, N. J., Gattás‐Asfura, K. M., Kar, S., & Stabler, C. L. (2019) · Journal of Diabetes Science and Technology · doi:10.1177/1932296819871947 · Cited by 24
“Additionally, an instant blood mediated inflammatory reaction (IBMIR) is instigated by both the inherent inflammatory nature of the donor islets’ surface as well as protein adsorption to the cellular graft upon blood contact.(15) This activation triggers complement and coagulation cascades, which, in turn, recruits in…”
BackgroundTissue‐engineering approaches in pancreatic islet transplantation
Pérez‐Basterrechea, M., Esteban, M. M., Vega, J. A., & Obaya, Á. J. (2018) · Biotechnology and Bioengineering · doi:10.1002/bit.26821 · Cited by 22
Impact of Procedure-Related Complications on Long-term Islet Transplantation Outcome
Caiazzo, R. J., Vantyghem, M., Raverdi, V., Bonner, C., Gmyr, V., Defrance, F., Leroy, C., Sergent, G., Hübert, T., Ernst, O., et al. (2014) · Transplantation · doi:10.1097/tp.0000000000000458 · Cited by 22
Shih, H., Mirmira, R. G., & Lin, C. (2014) · Journal of Materials Chemistry B · doi:10.1039/c4tb01593b · Cited by 26
Hughes, A., Mohanasundaram, D., Kireta, S., Jessup, C., Drogemuller, C., & Coates, P. (2013) · Transplantation · doi:10.1097/tp.0b013e31827fa453 · Cited by 21
“DISCUSSION Apoptosis is a major cause of islet cell loss in the early posttransplantation period (28, 29).”
BackgroundAn Isolated Venous Sac as a Novel Site for Cell Therapy in Diabetes Mellitus
Kakabadze, Z., Shanava, K., Ricordi, C., Shapiro, A. M. J., Gupta, S., & Berishvili, E. (2012) · Transplantation · doi:10.1097/tp.0b013e31825e4a83 · Cited by 21
“In the early loss of intraportally transplanted islets, contributors include low oxygen tension, cytokines/ chemokines released by immunologically active cells, such as Kupffer cells (macrophages) (16), and instant blood-mediated inflammatory reaction (17, 18).”
BackgroundPrevention of Early Loss of Transplanted Islets in the Liver of Mice by Adenosine
Nitta, T., Itoh, T., Matsuoka, N., Mera, T., Kojima, D., Nakano, M., Yamashita, Y., & Yasunami, Y. (2009) · Transplantation · doi:10.1097/tp.0b013e3181aa6c9b · Cited by 21
“Furthermore, it is important to clarify whether the adenosine receptor agonist such as ATL146e (29), which is currently being developed for clinical application, has any beneficial effect and how adenosine itself is effective in the improvement of the engraftment of transplanted islets in comparison to the other strat…”
ResultInnate immunity and heat shock response in islet transplantation
Lai, Y., Chen, C., & Linn, T. (2009) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2009.03899.x · Cited by 22
Schmidt, P., Magnusson, C., Lundgren, T., Korsgren, O., & Nilsson, B. (2008) · Transplantation · doi:10.1097/tp.0b013e3181890593 · Cited by 21
“(1) and has been shown to be triggered by tissue factor produced by the endocrine cells of the pancreas (2).”
BackgroundSelf-citationActivation of c-Jun NH2-terminal kinase during islet isolation.
Noguchi, H. (2007) · Endocrine journal · doi:10.1507/endocrj.kr-87 · Cited by 21
“inflammation reactions (IBMIR) [78, 82, 83] occur regularly during this procedure, even without clinical signs of intraportal thrombosis [77, 84].”
BackgroundIino, S., Abeyama, K., Kawahara, K., Yamakuchi, M., Hashiguchi, T., Matsukita, S., Yonezawa, S., Taniguchi, S., Nakata, M., Takao, S., et al. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-03-0750 · Cited by 21
“Likewise, an anticoagulant thrombomodulin, a coagulant tissue factor, was also expressed on islets, which might trigger the activation of an extrinsic blood coagulation cascade by the binding between factor VII and tissue factor (41).”
BackgroundIslet transplantation: where do we stand now?
Hirshberg, B., Rother, K. I., & Harlan, D. M. (2003) · Diabetes/Metabolism Research Reviews · doi:10.1002/dmrr.378 · Cited by 21
“mechanisms of islet survival post transplantation [14],”
Everwien, H., Keshi, E., Hillebrandt, K., Ludwig, B., Weinhart, M., Tang, P., Beierle, A., Napierala, H., Gassner, J., Seiffert, N., et al. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.09.022 · Cited by 20
Shrestha, P., Batra, L., Malik, M. T., Tan, M., Yolcu, E., & Shirwan, H. (2020) · American Journal of Transplantation · doi:10.1111/ajt.15958 · Cited by 20
Ramnath, R., Maillard, E., Jones, K., Bateman, P. A., Hughes, S., Gralla, J., Johnson, P. R. V., & Gray, D. (2015) · Cell Transplantation · doi:10.3727/096368914x685320 · Cited by 20
Immobilization of anticoagulant-loaded liposomes on cell surfaces by DNA hybridization.
Chen, H., Teramura, Y., & Iwata, H. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.07.002 · Cited by 20
Assessment of genetic factors for type 2 diabetes mellitus.
Yamada, Y., Matsuo, H., Segawa, T., Watanabe, S., Kato, K., Kameyama, T., Yokoi, K., Ichihara, S., Metoki, N., Yoshida, H., et al. (2006) · International Journal of Molecular Medicine · doi:10.3892/ijmm.18.2.299 · Cited by 20
Survival of the fittest? Natural selection in islet transplantation.
Smith, R. M., & Gale, E. (2005) · Transplantation · doi:10.1097/01.tp.0000157276.90986.fd · Cited by 20
“The immediate blood mediated inflammatory response may be said to have come of age in 2002 (3, 4) and a number of therapeutic strategies for its prevention have been proposed.”
BackgroundIkemoto, T., Tashiro, S., Yasutomo, K., Kishihara, K., Kurita, N., & Miyake, H. (2004) · Journal of Medical Investigation · doi:10.2152/jmi.51.178 · Cited by 20
Immunoprotection of cellular transplants for autoimmune type 1 diabetes through local drug delivery
Lansberry, T. R., & Stabler, C. L. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115179 · Cited by 20
Wang, C., Zhang, L.-D., Sun, Z., Yuan, X., Wu, B.-H., Cen, J., Cui, L., Zhang, K., Li, C. X., Wu, J., et al. (2022) · Hepatology · doi:10.1002/hep.32436 · Cited by 19
Nibbelink, M. G., Skrzypek, K., Karbaat, L., Both, S. K., Plass, J. R. M., Klomphaar, B., van Lente, J. J., Henke, S., Karperien, M., Stamatialis, D. F., et al. (2018) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-018-6178-6 · Cited by 20
Liuwantara, D., Chew, Y., Favaloro, E., Hawkes, J., Burns, H., O'Connell, P., & Hawthorne, W. (2016) · Transplantation Direct · doi:10.1097/txd.0000000000000590 · Cited by 19
“In clinical islet allotransplantation, IBMIR is a major cause of tissue loss, commencing on exposure of islet cells to blood after infusion into the portal vein.(7,8) It has been estimated that up to 60% of islets are lost within a week of transplantation.”
BackgroundInfluentialCirculating endothelial mediators in human pancreatitis-associated lung injury
Siemiątkowski, A., Wereszczyńska-Siemiątkowska, U., Mroczko, B., Galar, M., & Maziewski, T. (2015) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0000000000000338 · Cited by 19
IGF2: an endocrine hormone to improve islet transplant survival
Hughes, A., Rojas‐Canales, D. M., Drogemuller, C., Voelcker, N. H., Grey, S. T., & Coates, P. T. (2014) · Journal of Endocrinology · doi:10.1530/joe-13-0557 · Cited by 21
“…pathways and http://joe.endocrinology-journals.org 2014 Society for Endocrinology DOI: 10.1530/JOE-13-0557 Printed in Great Britain complement and infiltration of pro-inflammatory cytokines, such as interleukin-1b (IL1b) and interferon-g (IFNg) (Moberg et al. 2002, Johansson et al. 2005).”
BackgroundInfluentialHuman Pancreatic Islet Preparations Release HMGB1: (Ir)Relevance for Graft Engraftment
Nano, R., Racanicchi, L., Melzi, R., Mercalli, A., Maffi, P., Sordi, V., Ling, Z., Scavini, M., Korsgren, O., Celona, B., et al. (2012) · Cell Transplantation · doi:10.3727/096368912x657783 · Cited by 23
“This association was independent from the islet tissue factor expression (11,20), since its content was not different between preparations with high and low HMGB1 release.”
BackgroundSelf-citationMicrocoagulation processes after xenotransplantation
Chen, D.-X., & Dorling, A. (2005) · doi:10.1097/01.mot.0000174044.75567.d0 · Cited by 19
Allo Beta Cell transplantation: specific features, unanswered questions, and immunological challenge
Caldara, R., Tomajer, V., Monti, P., Sordi, V., Citro, A., Chimienti, R., Gremizzi, C., Catarinella, D., Tentori, S., Paloschi, V., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1323439 · Cited by 19
Kim, J., Jung, Y., Kim, S. H., Shin, J., Kim, S. H., & Park, C. (2018) · Xenotransplantation · doi:10.1111/xen.12441 · Cited by 18
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
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