Incompatibility between human blood and isolated islets of Langerhans: a finding with implications for clinical intraportal islet transplantation?
Abstract
The remarkable difference in success rates between clinical pancreas transplantation and islet transplantation is poorly understood. Despite the same histocompatibility barrier and similar immunosuppressive treatments in both transplantation procedures, human intraportal islet transplantation has a much inferior success rate than does vascularized pancreas transplantation. Thus far, little attention has been directed to the possibility that islets transplanted into the blood stream may elicit an injurious incompatibility reaction. We have tested this hypothesis in vitro with human islets and in vivo with porcine islets. Human islets were exposed to nonanticoagulated human ABO-compatible blood in surface-heparinized polyvinyl chloride tubing loops. Heparin and/or the soluble complement receptor 1 (sCR1) TP10 were tested as additives. Adult porcine islets were transplanted intraportally into pigs, and the liver was recovered after 60 min for immunohistochemical staining. Human islets induced a rapid consumption and activation of platelets. Neutrophils and monocytes were also consumed, and the coagulation and complement systems were activated. Upon histological examination, islets were found to be embedded in clots and infiltrated with CD11+ leukocytes. Furthermore, the cellular morphology was disrupted. When heparin and sCR1 were added to the blood, these events were avoided. Porcine islets retrieved in liver biopsies after intraportal islet allotransplantation showed a morphol…
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Leukocytes infiltrate the islets within an hour, leading to cell death.
“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 [140]
One consequence of direct blood contact during portal vein islet infusion is an immune response called the instant blood-mediated inflammatory reaction (IBMIR).
“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 [140]
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.
“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 [140]
Within 15 minutes of contact with host blood, islets are encapsulated within a layer of platelets, reducing nutrient diffusion.
“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 [140]
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Cited by 431
- Authors
- Bennet, W., Sundberg, B., Groth, C. G., Brendel, M. D., Brandhorst, D., Brandhorst, H., Bretzel, R. G., Elgue, G., Larsson, R., Nilsson, B., & Korsgren, O.
- Affiliations
- Karolinska Institutet (SE)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1999-10-01
- Volume
- 48
- Issue
- 10
- Pages
- 1907-1914
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2066808970
- Cited by
- 431
- References
- 0
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 11 · 2023: 7 · 2022: 9 · 2021: 17 · 2020: 12 · 2019: 23 · 2018: 17 · 2017: 16 · 2016: 31 · 2015: 24 · 2014: 18 · 2013: 24 · 2012: 17
- FWCI
- 8.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- islet transplantation, intraportal islet transplantation, islet damage, platelet activation, neutrophil activation, monocyte activation, coagulation activation, complement activation, soluble complement receptor 1, heparin, porcine islets, allogeneic islet transplantation
- MeSH terms
- Adult, Animals, Blood, Enzyme-Linked Immunosorbent Assay, Female, Humans, Inflammation, Insulin, Islets of Langerhans, Leukocyte Count, Male, Middle Aged, Platelet Count, Portal Vein, Rabbits, Swine, Islets of Langerhans Transplantation
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