Stem Cell Microarrays for Assessing Growth Factor Signaling in Engineered Glycan Microenvironments.
Stem Cell Microarrays for Assessing Growth Factor Signaling in Engineered Glycan Microenvironments.
复制标题
DOI：
10.1002/adhm.202101232
复制
发表时间：
2022-03
影响因子：
10
通讯作者：
Godula K
中科院分区：
文献类型：
--
作者：
Michalak AL;Trieger GW;Trieger KA;Godula K
细胞外聚糖，如糖胺聚糖（GAG），在组织的发育和维持过程中提供了一个必不可少的调节组分。GAG具有一系列生长因子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，并在细胞表面呈现时促进活性信号复合物的形成。因此，GAG已被用作生物活性组分，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组成异质性使得难以建立这类聚糖的结构-功能关系。在这里，我们描述了一个干细胞阵列平台，其中化学修饰的类肝素GAG多糖缀合至明胶基质并引入聚丙烯酰胺水凝胶网络中。该阵列允许直接分析HS对小鼠胚胎干细胞中通过FGF 2依赖性有丝分裂原活化蛋白激酶（MAPK）途径的信号传导的贡献。随着最近出现的强大的合成和重组技术，以产生明确的GAG结构，一个平台，用于分析生长因子的结合和信号，响应于这些生物分子的存在，将提供一个强大的工具，整合到生物材料的聚糖，以提高其生物学特性和应用。本研究将糖胺聚糖-蛋白质结合物整合到水凝胶支持的干细胞微阵列平台中，以分析细胞外聚糖在生长因子信号传导中的活性。这样的平台可以实现用于基于干细胞的再生疗法的功能性糖材料的快速开发和优化。
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 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, we describe a stem cell array platform, in which chemically modified heparinoid GAG polysaccharides were 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. The present study describes the integration of glycosaminoglycan-protein conjugates into a hydrogel-supported stem cell microarray platform to analyze the activity of extracellular glycans in growth factor signaling. Such platforms can enable rapid development and optimization of functional glycomaterials for stem cell-based regenerative therapies.
登录
查看更多内容
影响因子：
14
作者：
Seo J;Shin JY;Leijten J;Jeon O;Camci-Unal G;Dikina AD;Brinegar K;Ghaemmaghami AM;Alsberg E;Khademhosseini A
通讯作者：
Khademhosseini A
DOI：
10.1073/pnas.0705807105
发表时间：
2008-03-25
影响因子：
11.1
作者：
Presto, Jenny;Thuveson, Maria;Kjellen, Lena
通讯作者：
Kjellen, Lena
影响因子：
14.8
作者：
Brafman, David A.;Chien, Shu;Willert, Karl
通讯作者：
Willert, Karl
影响因子：
2.9
作者：
Sterner, Eric;Meli, Luciana;Kwon, Seok-Joon;Dordick, Jonathan S.;Linhardt, Robert J.
通讯作者：
Linhardt, Robert J.
影响因子：
5.5
作者：
Sodhi H;Panitch A
通讯作者：
Panitch A