Osteogenic differentiation of human mesenchymal stem cells directed by extracellular matrix-mimicking ligands in a biomimetic self-assembled peptide amphiphile nanomatrix.
Osteogenic differentiation of human mesenchymal stem cells directed by extracellular matrix-mimicking ligands in a biomimetic self-assembled peptide amphiphile nanomatrix.
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DOI：
10.1021/bm9007452
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发表时间：
2009-10-12
影响因子：
6.2
通讯作者：
Jun, Ho-Wook
中科院分区：
文献类型：
--
作者：
Anderson, Joel M.;Kushwaha, Meenakshi;Tambralli, Ajay;Bellis, Susan L.;Camata, Renato P.;Jun, Ho-Wook
本研究调查的能力，纳米级，仿生肽两亲物（PA）的支架与特定的细胞粘附配体直接成骨分化的人骨髓间充质干细胞（hMSCs）没有成骨补充。合成PA序列以模拟天然骨细胞外基质（ECM），表达不同的分离配体（即RGDS、DGEA、KRSR）。所有PA均呈现为用于接种的hMSC的自组装二维涂层。初步的附着结果表明，不同的PA可以单独识别的基础上纳入粘合剂配体。长期研究评估了长达35天的成骨分化。含有RGDS的PA纳米基质表达显著更高的碱性磷酸酶（ALP）活性，表明早期促进成骨分化。向成骨形态和阳性染色的矿物质沉积的渐进转变提供了进一步确认的RGDS含有PA纳米基质。总体而言，PA纳米基质显然在无需补充剂的帮助下通过模拟天然ECM来指导hMSC的成骨分化方面具有巨大的前景，提供了一个可适应的环境，允许不同的粘附配体控制细胞行为。该研究模型通过密切遵循自然组织形成的原则，建立了一种新的多功能方法来再生骨组织。
This study investigated the ability of nanoscale, biomimetic peptide amphiphile (PA) scaffolds inscribed with specific cellular adhesive ligands to direct the osteogenic differentiation of human mesenchymal stem cells (hMSCs) without osteogenic supplements. PA sequences were synthesized to mimic the native bone extracellular matrix (ECM), expressing different isolated ligands (i.e. RGDS, DGEA, KRSR). All PAs were presented as self-assembled two-dimensional coatings for the seeded hMSCs. Initial attachment results demonstrated that the different PAs could be individually recognized based on the incorporated adhesive ligands. Long-term studies assessed osteogenic differentiation up to 35 days. The RGDS-containing PA nanomatrix expressed significantly greater alkaline phosphatase (ALP) activity, indicating the early promotion of osteogenic differentiation. A progressive shift towards osteogenic morphology and positive staining for mineral deposition provided further confirmation of the RGDS-containing PA nanomatrix. Overall, the PA nanomatrix clearly has great promise for directing the osteogenic differentiation of hMSCs without the aid of supplements by mimicking the native ECM, providing an adaptable environment that allows for different adhesive ligands to control cellular behaviors. This research model establishes the beginnings of a new versatile approach to regenerate bone tissues by closely following the principles of natural tissue formation.
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