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 501–503 of 503
Remaining Challenges and Clinical Perspectives
Domínguez‐Bendala, J. (2009) · Humana Press eBooks · doi:10.1007/978-1-60761-132-5_8
47 – Islet Cell Transplantation
Emamaullee, J., & Shapiro, A. M. J. (2008) · Elsevier eBooks · doi:10.1016/b978-012369410-2.50049-8
The Role of Complement in Transplantation
Kirschfink, M., & Mollnes, T. (2004) · Kluwer Academic Publishers eBooks · doi:10.1007/1-4020-8056-5_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
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
