Crosslinked Layered Surfaces of Heparin and Poly(L-Lysine) Enhance Mesenchymal Stromal Cell Behavior in the Presence of Soluble Interferon Gamma.

IF 2.9 4区 生物学 Q1 ANATOMY & MORPHOLOGY
Mahsa Haseli, Luis Pinzon-Herrera, Jorge Almodovar
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引用次数: 0

Abstract

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.

在可溶性干扰素γ存在下,肝素和聚l -赖氨酸的交联层状表面增强间充质间质细胞的行为。
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性疾病。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多层肝素和聚l -赖氨酸(HEP/PLL)作为可溶性干扰素γ (IFN-γ)刺激的hMSCs的生物活性表面。通过层层组装形成多层,HEP为最后一层,在培养基中补充IFN-γ。通过Azure A染色、石英晶体微天平和x射线光电子能谱证实了多层结构和化学性质。评估hMSCs的粘附、活力和分化。结果表明(HEP/PLL)多层膜对hMSCs的粘附性较差。然而,使用1-乙基-3-(3-二甲氨基丙基)碳二亚胺和n -羟基琥珀酰亚胺进行化学交联可显著增强hMSCs的粘附性和活力。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存在的交联(HEP/PLL)多层膜上培养的hMSCs成功分化为成骨和脂肪谱系,茜素红、油红O染色以及碱性磷酸酶活性证实了这一点。本研究提示交联(HEP/PLL)膜可以调节hMSCs对可溶性因子的反应,这可能改善基于hMSCs的治疗方法,旨在治疗多种免疫疾病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cells Tissues Organs
Cells Tissues Organs 生物-发育生物学
CiteScore
4.90
自引率
3.70%
发文量
45
审稿时长
6-12 weeks
期刊介绍: ''Cells Tissues Organs'' aims at bridging the gap between cell biology and developmental biology and the emerging fields of regenerative medicine (stem cell biology, tissue engineering, artificial organs, in vitro systems and transplantation biology). CTO offers a rapid and fair peer-review and exquisite reproduction quality. Special topic issues, entire issues of the journal devoted to a single research topic within the range of interests of the journal, are published at irregular intervals.
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