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引导 hMSC 黏附和在支撑脂质双层上分化。

Guiding hMSC Adhesion and Differentiation on Supported Lipid Bilayers.

机构信息

Bioinspired Molecular Engineering Laboratory, MIRA Institute for Biomedical Technology, Technical Medicine and Molecular Nanofabrication Group, MESA+ Institute for Nanotechnology, University of Twente, 7500, AE, Enschede, The Netherlands.

出版信息

Adv Healthc Mater. 2017 Feb;6(3). doi: 10.1002/adhm.201600862. Epub 2016 Nov 28.

Abstract

Mesenchymal stem cells (MSCs) are intensively investigated for regenerative medicine applications due to their ease of isolation and multilineage differentiation capacity. Hence, designing instructive microenvironments to guide MSC behavior is important for the generation of smart interfaces to enhance biomaterial performance in guiding desired tissue formation. Supported lipid bilayers (SLBs) as cell membrane mimetics can be employed as biological interfaces with easily tunable characteristics such as biospecificity, mobility, and density of predesigned ligand molecules. Arg-Gly-Asp (RGD) ligand functionalized SLBs are explored for guiding human MSC (hMSC) adhesion and differentiation by studying the effect of changes in ligand density and mobility. Cellular and molecular analyses show that adhesion occurs through specific interactions with RGD ligands where the extent is positively correlated to changes in ligand density. Furthermore, cell area is significantly regulated by ligand density on ligand-mobile SLBs when compared to ligand-immobile SLBs. Finally, the osteogenic differentiation capacity of hMSCs is positively correlated to ligand density on ligand-mobile SLBs indicating that regulation of cell spreading is linked to cell differentiation capacity. These results demonstrate that hMSC behavior can be directed on SLBs by molecular design and presents SLBs as versatile platforms for future engineering of smart biomaterial coatings.

摘要

间充质干细胞(MSCs)由于其易于分离和多能分化能力,被广泛研究用于再生医学应用。因此,设计有指导意义的微环境来引导 MSC 行为对于生成智能界面以增强生物材料在引导所需组织形成方面的性能非常重要。支持脂质双层(SLB)作为细胞膜模拟物,可以用作具有易于调节的特性的生物界面,例如生物特异性、流动性和预定配体分子的密度。通过研究配体密度和流动性变化对人 MSC(hMSC)黏附和分化的影响,探索了 Arg-Gly-Asp(RGD)配体功能化的 SLB 来指导细胞黏附和分化。细胞和分子分析表明,黏附是通过与 RGD 配体的特异性相互作用发生的,其程度与配体密度的变化呈正相关。此外,与配体固定的 SLB 相比,配体可动的 SLB 上的配体密度显著调节细胞面积。最后,hMSCs 的成骨分化能力与配体可动的 SLB 上的配体密度呈正相关,表明细胞扩展的调节与细胞分化能力相关。这些结果表明,hMSC 行为可以通过分子设计在 SLB 上进行指导,并将 SLB 呈现为未来智能生物材料涂层的多功能平台。

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