Fully Synthetic Heparan Sulfate-Based Neural Tissue Construct That Maintains the Undifferentiated State of Neural Stem Cells
Fully Synthetic Heparan Sulfate-Based Neural Tissue Construct That Maintains the Undifferentiated State of Neural Stem Cells
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DOI：
10.1021/acschembio.9b00401
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发表时间：
2019-09-01
影响因子：
4
通讯作者：
Boons, Geert-Jan
中科院分区：
文献类型：
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作者：
Chopra, Pradeep;Logun, Meghan T.;Boons, Geert-Jan
肝素和硫酸乙酰肝素（HS）是用于构建生物材料的有吸引力的组分，因为它们能够募集和调节生长因子的活性。然而，天然来源的肝素和HS的结构和功能异质性是制备用于再生医学的生物材料的障碍。为了解决这个问题，我们已经制备了由定义明确的合成HS衍生的二糖改性的水凝胶。包封在聚乙二醇基水凝胶中的人诱导多能细胞衍生的神经干细胞（HIP-NSC）表现出增殖和自我更新的显著增加，所述水凝胶由作为成纤维细胞生长因子-2（FGF-2）的已知配体的侧链HS二糖修饰。这一观察结果很重要，因为有证据表明，未分化的干细胞可以通过其旁分泌信号机制产生显着的治疗效果。我们的数据表明，HS二糖保护FGF-2，它具有非常短的生物半衰期，从降解。预期通过仔细选择合成HS寡糖，将有可能控制特定生长因子的保留和释放，这反过来将提供对细胞命运的控制。
Heparin and heparan sulfate (HS) are attractive components for constructing biomaterials due to their ability to recruit and regulate the activity of growth factors. The structural and functional heterogeneity of naturally derived heparin and HS is, however, an impediment for the preparation of biomaterials for regenerative medicine. To address this problem, we have prepared hydrogels modified by well-defined synthetic HS-derived disaccharides. Human induced pluripotent cell-derived neural stem cells (HIP-NSCs) encapsulated in a polyethylene glycol-based hydrogel modified by a pendent HS disaccharide that is a known ligand for fibroblast growth factor-2 (FGF-2) exhibited a significant increase in proliferation and self-renewal. This observation is important because evidence is emerging that undifferentiated stems cells can yield significant therapeutic benefits via their paracrine signaling mechanisms. Our data indicate that the HS disaccharide protects FGF-2, which has a very short biological half-live, from degradation. It is anticipated that, by careful selection of a synthetic HS oligosaccharide, it will be possible to control retention and release of specific growth factor, which in turn will provide control over cell fate.