Stem Cell Microarrays for Assessing Growth Factor Signaling in Engineered Glycan Microenvironments,Advanced Healthcare Materials

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Stem Cell Microarrays for Assessing Growth Factor Signaling in Engineered Glycan Microenvironments
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2021-09-20 , DOI: 10.1002/adhm.202101232
Austen L Michalak ₁ , Greg W Trieger ₁ , Kelsey A Trieger ₁ , Kamil Godula _{1,

2}

Affiliation

Extracellular glycans, such as glycosaminoglycans (GAGs), provide an essential regulatory component during the development and maintenance of tissues. GAGs, which harbor binding sites for a range of growth factors (GFs) and other morphogens, help establish gradients of these molecules in the extracellular matrix (ECM) and promote the formation of active signaling complexes when presented at the cell surface. As such, GAGs have been pursued as biologically active components for the development of biomaterials for cell-based regenerative therapies. However, their structural complexity and compositional heterogeneity make establishing structure-function relationships for this class of glycans difficult. Here, a stem cell array platform is described, in which chemically modified heparan sulfate (HS) GAG polysaccharides are conjugated to a gelatin matrix and introduced into a polyacrylamide hydrogel network. This array allowed for direct analysis of HS contributions to the signaling via the FGF2-dependent mitogen activated protein kinase (MAPK) pathway in mouse embryonic stem cells. With the recent emergence of powerful synthetic and recombinant technologies to produce well-defined GAG structures, a platform for analyzing both growth factor binding and signaling in response to the presence of these biomolecules will provide a powerful tool for integrating glycans into biomaterials to advance their biological properties and applications.

中文翻译：

用于评估工程聚糖微环境中生长因子信号传导的干细胞微阵列

细胞外聚糖，例如糖胺聚糖 (GAG)，在组织的发育和维持过程中提供了重要的调节成分。GAG 含有一系列生长因子 (GF) 和其他形态发生素的结合位点，有助于在细胞外基质 (ECM) 中建立这些分子的梯度，并在细胞表面出现时促进活性信号复合物的形成。因此，GAG 已被用作生物活性成分，用于开发用于基于细胞的再生疗法的生物材料。然而，它们的结构复杂性和成分异质性使得建立这类聚糖的结构-功能关系变得困难。在这里，描述了一个干细胞阵列平台，其中化学改性的硫酸乙酰肝素 (HS) GAG 多糖与明胶基质结合并引入聚丙烯酰胺水凝胶网络中。该阵列允许通过小鼠胚胎干细胞中的 FGF2 依赖性丝裂原活化蛋白激酶 (MAPK) 途径直接分析 HS 对信号传导的贡献。随着最近出现的用于产生明确定义的 GAG 结构的强大合成和重组技术的出现，用于分析生长因子结合和响应这些生物分子存在的信号传导的平台将为将聚糖整合到生物材料中以推进其生物属性和应用。该阵列允许通过小鼠胚胎干细胞中的 FGF2 依赖性丝裂原活化蛋白激酶 (MAPK) 途径直接分析 HS 对信号传导的贡献。随着最近出现的用于产生明确定义的 GAG 结构的强大合成和重组技术的出现，用于分析生长因子结合和响应这些生物分子存在的信号传导的平台将为将聚糖整合到生物材料中以推进其生物属性和应用。该阵列允许通过小鼠胚胎干细胞中的 FGF2 依赖性丝裂原活化蛋白激酶 (MAPK) 途径直接分析 HS 对信号传导的贡献。随着最近出现的用于产生明确定义的 GAG 结构的强大合成和重组技术的出现，用于分析生长因子结合和响应这些生物分子存在的信号传导的平台将为将聚糖整合到生物材料中以推进其生物属性和应用。

更新日期：2021-09-20

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