Type 1 diabetes mellitus (T1DM) does not affect whole blood responses to alginate-based microspheres despite plasma lipid and glucose differences

Encapsulation of insulin-producing cells holds significant therapeutic potential for treating type 1 diabetes (T1DM). The impact of diabetic conditions on host responses is not well understood. This study is the first to compare ex-vivo whole blood responses to alginate microbeads in T1DM subjects v...

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Main Authors: Kalaiyarasi Vasuthas, Sverre Christian Christiansen, Joachim Sebastian Kjesbu, Liv Ryan, Trygve Andreassen, Geir Slupphaug, Berit L. Strand, Jørgen Stenvik, Anne Mari A. Rokstad
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425006830
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author Kalaiyarasi Vasuthas
Sverre Christian Christiansen
Joachim Sebastian Kjesbu
Liv Ryan
Trygve Andreassen
Geir Slupphaug
Berit L. Strand
Jørgen Stenvik
Anne Mari A. Rokstad
author_facet Kalaiyarasi Vasuthas
Sverre Christian Christiansen
Joachim Sebastian Kjesbu
Liv Ryan
Trygve Andreassen
Geir Slupphaug
Berit L. Strand
Jørgen Stenvik
Anne Mari A. Rokstad
author_sort Kalaiyarasi Vasuthas
collection DOAJ
description Encapsulation of insulin-producing cells holds significant therapeutic potential for treating type 1 diabetes (T1DM). The impact of diabetic conditions on host responses is not well understood. This study is the first to compare ex-vivo whole blood responses to alginate microbeads in T1DM subjects versus healthy controls.Nineteen T1DM and 27 healthy controls were included. Alginate microbeads varying in guluronic acid content (68 % and 47 % G), sulfated alginate/alginate ratios (10/90 and 20/80), or containing poly-L-lysine were characterised regarding activation of coagulation, complement, and inflammatory cytokine release in whole blood. Responses to heat-killed microbes (E. coli, S. pneumoniae, M. tuberculosis, and C. albicans) and immune agonists (TLR ligands, T-cell stimulant, and Dectin ligand) were also compared.NMR spectroscopy identified 40 altered lipoproteins and metabolites in plasma in T1DM vs. controls. However, whole blood responses were strikingly similar, indicating that metabolic alterations in T1DM are not accompanied by differences in inflammatory capacity.When merging all subjects, PCA clustered microbead responses into three groups of alginates, sulfated alginates, and poly-L-lysine-coated alginate (AP), respectively. Pairwise comparison by multiple t-tests identified significant changes in inflammatory mediators between the main groups; alginate microbeads differentially induced 25 out of 29 mediators compared to AP microbeads and 18 mediators compared to sulfated alginate microbeads. Alginate microbeads with distinct guluronic acid content (68 % vs 47 % G) revealed no significant differences. These findings indicate that the material properties are the most important determinants of the host inflammatory responses in blood, which are not changed in well-controlled T1DM.
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spelling doaj-art-271ed1e6103a422483d8fa998585c3032025-08-20T03:56:41ZengElsevierMaterials Today Bio2590-00642025-10-013410211310.1016/j.mtbio.2025.102113Type 1 diabetes mellitus (T1DM) does not affect whole blood responses to alginate-based microspheres despite plasma lipid and glucose differencesKalaiyarasi Vasuthas0Sverre Christian Christiansen1Joachim Sebastian Kjesbu2Liv Ryan3Trygve Andreassen4Geir Slupphaug5Berit L. Strand6Jørgen Stenvik7Anne Mari A. Rokstad8Center of Molecular Inflammation Research (CEMIR), NTNU, Norway; Department of Clinical and Molecular Medicine, NTNU, NorwayDepartment of Clinical and Molecular Medicine, NTNU, Norway; Department of Endocrinology, St Olav's Hospital, Trondheim University Hospital, Trondheim, NorwayDepartment of Biotechnology and Food Science, NTNU, NorwayCenter of Molecular Inflammation Research (CEMIR), NTNU, Norway; Department of Clinical and Molecular Medicine, NTNU, NorwayDepartment of Circulation and Medical Imaging, NTNU, Trondheim, Norway; Central Staff, St. Olavs Hospital HF, Trondheim, NorwayDepartment of Clinical and Molecular Medicine, NTNU, Norway; Clinic of Laboratory Medicine, St Olavs Hospital, Trondheim, NorwayDepartment of Biotechnology and Food Science, NTNU, NorwayCenter of Molecular Inflammation Research (CEMIR), NTNU, Norway; Department of Clinical and Molecular Medicine, NTNU, Norway; Clinic of Anaesthesia and Intensive Care, St. Olavs Hospital, Trondheim University Hospital, Trondheim, NorwayCenter of Molecular Inflammation Research (CEMIR), NTNU, Norway; Department of Clinical and Molecular Medicine, NTNU, Norway; Clinic of Laboratory Medicine, St Olavs Hospital, Trondheim, Norway; Corresponding author. Center of Molecular Inflammation Research (CEMIR), NTNU, NorwayEncapsulation of insulin-producing cells holds significant therapeutic potential for treating type 1 diabetes (T1DM). The impact of diabetic conditions on host responses is not well understood. This study is the first to compare ex-vivo whole blood responses to alginate microbeads in T1DM subjects versus healthy controls.Nineteen T1DM and 27 healthy controls were included. Alginate microbeads varying in guluronic acid content (68 % and 47 % G), sulfated alginate/alginate ratios (10/90 and 20/80), or containing poly-L-lysine were characterised regarding activation of coagulation, complement, and inflammatory cytokine release in whole blood. Responses to heat-killed microbes (E. coli, S. pneumoniae, M. tuberculosis, and C. albicans) and immune agonists (TLR ligands, T-cell stimulant, and Dectin ligand) were also compared.NMR spectroscopy identified 40 altered lipoproteins and metabolites in plasma in T1DM vs. controls. However, whole blood responses were strikingly similar, indicating that metabolic alterations in T1DM are not accompanied by differences in inflammatory capacity.When merging all subjects, PCA clustered microbead responses into three groups of alginates, sulfated alginates, and poly-L-lysine-coated alginate (AP), respectively. Pairwise comparison by multiple t-tests identified significant changes in inflammatory mediators between the main groups; alginate microbeads differentially induced 25 out of 29 mediators compared to AP microbeads and 18 mediators compared to sulfated alginate microbeads. Alginate microbeads with distinct guluronic acid content (68 % vs 47 % G) revealed no significant differences. These findings indicate that the material properties are the most important determinants of the host inflammatory responses in blood, which are not changed in well-controlled T1DM.http://www.sciencedirect.com/science/article/pii/S2590006425006830Alginate microspheresLipoproteinsSulfated alginateImmune responseT1DMWhole blood model
spellingShingle Kalaiyarasi Vasuthas
Sverre Christian Christiansen
Joachim Sebastian Kjesbu
Liv Ryan
Trygve Andreassen
Geir Slupphaug
Berit L. Strand
Jørgen Stenvik
Anne Mari A. Rokstad
Type 1 diabetes mellitus (T1DM) does not affect whole blood responses to alginate-based microspheres despite plasma lipid and glucose differences
Materials Today Bio
Alginate microspheres
Lipoproteins
Sulfated alginate
Immune response
T1DM
Whole blood model
title Type 1 diabetes mellitus (T1DM) does not affect whole blood responses to alginate-based microspheres despite plasma lipid and glucose differences
title_full Type 1 diabetes mellitus (T1DM) does not affect whole blood responses to alginate-based microspheres despite plasma lipid and glucose differences
title_fullStr Type 1 diabetes mellitus (T1DM) does not affect whole blood responses to alginate-based microspheres despite plasma lipid and glucose differences
title_full_unstemmed Type 1 diabetes mellitus (T1DM) does not affect whole blood responses to alginate-based microspheres despite plasma lipid and glucose differences
title_short Type 1 diabetes mellitus (T1DM) does not affect whole blood responses to alginate-based microspheres despite plasma lipid and glucose differences
title_sort type 1 diabetes mellitus t1dm does not affect whole blood responses to alginate based microspheres despite plasma lipid and glucose differences
topic Alginate microspheres
Lipoproteins
Sulfated alginate
Immune response
T1DM
Whole blood model
url http://www.sciencedirect.com/science/article/pii/S2590006425006830
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