Crosslinked layered surfaces of heparin and poly(L-lysine) enhance mesenchymal stromal cells behavior in the presence of soluble interferon gamma
Crosslinked layered surfaces of heparin and poly(L-lysine) enhance mesenchymal stromal cells behavior in the presence of soluble interferon gamma
复制标题
肝素和聚（L-赖氨酸）的交联层状表面在可溶性干扰素γ存在下增强间充质基质细胞的行为
DOI：
10.1159/000521609
复制
发表时间：
2021
影响因子：
2.7
通讯作者：
Almodovar, Jorge
中科院分区：
文献类型：
--
作者：
Haseli, Mahsa;Pinzon-Herrera, Luis;Almodovar, Jorge
人间充质基质细胞（hMSCs）是一种多能细胞，已被提出用于治疗免疫介导的疾病。在组织培养塑料上培养hMSCs会降低其治疗潜力，部分原因是缺乏细胞外基质成分。本研究的目的是评估肝素和聚（L-赖氨酸）（HEP/PLL）的多层膜作为可溶性干扰素γ（IFN-γ）刺激的hMSCs的生物活性表面。通过逐层组装形成多层，其中HEP作为最终层并在培养基中补充有IFN-γ。使用天青A染色，石英晶体微量天平，和X射线光电子能谱法证实多层结构和化学。评估hMSC粘附、活力和分化。结果表明，（HEP/PLL）多层涂层对hMSCs的粘附性较差。然而，使用1-乙基-3-（3-二甲基氨基丙基）碳二亚胺和N-羟基琥珀酰亚胺进行化学交联显著增强了hMSCs的粘附和活力。通过测定吲哚胺2，3-双加氧酶活性，证实了在交联（HEP/PLL）多层膜上培养的hMSCs的免疫抑制特性。最后，在可溶性IFN-γ存在下，在交联（HEP/PLL）多层膜上培养的hMSC成功地向成骨和成脂谱系分化，如通过茜素红和油红O染色以及碱性磷酸酶活性所证实的。这项研究表明，交联（HEP/PLL）膜可以调节hMSCs对可溶性因子的反应，这可能会改善旨在治疗几种免疫疾病的基于hMSCs的疗法。
Human mesenchymal stromal cells (hMSCs) are multipotent cells that have been proposed for the treatment of immune-mediated diseases. Culturing hMSCs on tissue culture plastic reduces their therapeutic potential in part due to the lack of extracellular matrix components. The aim of this study is to evaluate multilayers of heparin and poly (L-lysine)(HEP/PLL) as a bioactive surface for hMSCs stimulated with soluble interferon gamma (IFN-γ). Multilayers were formed, via layer-by-layer assembly, with HEP as the final layer and supplemented with IFN-γ in the culture medium. Multilayer construction and chemistry were confirmed using Azure A staining, quartz crystal microbalance, and X-ray photoelectron spectroscopy. hMSCs adhesion, viability, and differentiation, were assessed. Results showed that (HEP/PLL) multilayer coatings were poorly adhesive for hMSCs. However, performing chemical crosslinking using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide significantly enhanced hMSCs adhesion and viability. The immunosuppressive properties of hMSCs cultured on crosslinked (HEP/PLL) multilayers were confirmed by measuring indoleamine 2, 3-dioxygenase activity. Lastly, hMSCs cultured on crosslinked (HEP/PLL) multilayers in the presence of soluble IFN-γ successfully differentiated towards the osteogenic and adipogenic lineages as confirmed by Alizarin red, and oil-red O staining, as well as alkaline phosphatase activity. This study suggests that crosslinked (HEP/PLL) films can modulate hMSCs response to soluble factors, which may improve hMSCs-based therapies aimed at treating several immune diseases.