Vasuthas Kalaiyarasi, Christiansen Sverre Christian, Kjesbu Joachim Sebastian, Ryan Liv, Andreassen Trygve, Slupphaug Geir, Strand Berit L, Stenvik Jørgen, Rokstad Anne Mari A
Center of Molecular Inflammation Research (CEMIR), NTNU, Norway.
Department of Clinical and Molecular Medicine, NTNU, Norway.
Mater Today Bio. 2025 Jul 18;34:102113. doi: 10.1016/j.mtbio.2025.102113. eCollection 2025 Oct.
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 (, , , and ) 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.
封装产胰岛素细胞在治疗1型糖尿病（T1DM）方面具有巨大的治疗潜力。糖尿病状况对宿主反应的影响尚未得到充分了解。本研究首次比较了T1DM患者与健康对照者对藻酸盐微珠的体外全血反应。纳入了19名T1DM患者和27名健康对照者。对不同古洛糖醛酸含量（68%和47% G）、硫酸化藻酸盐/藻酸盐比例（10/90和20/80）或含有聚-L-赖氨酸的藻酸盐微珠进行了全血中凝血、补体激活及炎症细胞因子释放的特性分析。还比较了对热灭活微生物（、、和）及免疫激动剂（Toll样受体配体、T细胞刺激剂和Dectin配体）的反应。核磁共振波谱法鉴定出T1DM患者与对照者血浆中有40种脂蛋白和代谢物发生改变。然而，全血反应惊人地相似，表明T1DM中的代谢改变并未伴随炎症能力的差异。将所有受试者合并后，主成分分析将微珠反应分别聚为藻酸盐、硫酸化藻酸盐和聚-L-赖氨酸包被藻酸盐（AP）三组。通过多次t检验进行成对比较发现，主要组之间炎症介质有显著变化；与AP微珠相比，藻酸盐微珠在29种介质中有25种差异诱导，与硫酸化藻酸盐微珠相比有18种介质差异诱导。不同古洛糖醛酸含量（68% G对47% G）的藻酸盐微珠未显示出显著差异。这些发现表明，材料特性是血液中宿主炎症反应的最重要决定因素，在病情得到良好控制的T1DM中这些因素并未改变。
