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A comparative in vitro study of the effect of biospecific integrin recognition processes and substrate nanostructure on stem cell 3D spheroid formation.
Journal of Materials Science: Materials in Medicine ( IF 3.7 ) Pub Date : 2020-03-23 , DOI: 10.1007/s10856-020-06373-x
Valeria Perugini 1 , Matteo Santin 1
Affiliation  

The in vitro study of the properties of the human mesenchymal stem cells as well as their manipulation in culture for clinical purposes depends on the elimination of artefacts caused by the lack of their natural environment. It is now widely accepted that mesenchymal stem cells should be studied when they are organised as 3D spheroids rather than fibroblast-like colonies. Although this can be achieved with the use of some extracellular matrix proteins or by non-adherent conditions these suffer of significant limitations. The recent development of synthetic substrates resembling the physicochemical and biochemical properties of the adult stem cell niche has prompted questions about the role played by nanotopography and receptor-mediated adhesion. In the present paper, the influence of two types of substrates bearing the same nanostructure, but exposing either a non-specific or an integrin-specific binding motif was studied. Carboxybetaine-tethered hyperbranched poly(ɛ-lysine) dendrons showed that the hyperbranched structure was fundamental to induce spheroid formation, but these were forming more slowly, were of reduced size and less stable than those growing on substrates based on the same hyperbranched structures that had been functionalised at their uppermost branching generation by a laminin amino acid sequence, i.e. YIGSR. The study shows that both nanostructure and biorecognition need to be combined to achieve a substrate for stem cell spheroid formation as that observed in vivo in the adult stem cell niche.

中文翻译:

生物特异性整联蛋白识别过程和底物纳米结构对干细胞3D球体形成的影响的体外比较研究。

人间充质干细胞的性质及其在临床上的培养操作的体外研究取决于消除由于缺乏天然环境而导致的伪影。现在,广泛公认的是,当间充质干细胞组织为3D球体而不是成纤维细胞样菌落时,应进行研究。尽管这可以通过使用某些细胞外基质蛋白或通过非粘附条件来实现,但这些方法存在明显的局限性。类似于成人干细胞小生境的理化和生化特性的合成底物的最新发展,引发了有关纳米形貌和受体介导的粘附作用的质疑。在本文中,两种具有相同纳米结构的基材的影响 但是研究了暴露非特异性或整联蛋白特异性的结合基序。羧基甜菜碱束缚的超支化聚(γ-赖氨酸)树突表明,超支化结构是诱导球状体形成的基础,但与基于相同的超支化结构的底物上生长的那些相比,它们形成速度较慢,尺寸减小且稳定性较差通过层粘连蛋白氨基酸序列,即YIGSR,在它们的最上面的分支世代被功能化。研究表明,纳米结构和生物识别都需要结合起来,以实现干细胞球体形成的基质,就像在成人干细胞生态位中体内观察到的那样。羧基甜菜碱束缚的超支化聚(γ-赖氨酸)树突表明,超支化结构是诱导球状体形成的基础,但与基于相同的超支化结构的底物上生长的那些相比,它们形成速度较慢,尺寸减小且稳定性较差通过层粘连蛋白氨基酸序列,即YIGSR,在它们的最上面的分支世代被功能化。研究表明,纳米结构和生物识别都需要结合起来,以实现干细胞球体形成的基质,就像在成人干细胞小生境中在体内观察到的那样。羧基甜菜碱束缚的超支化聚(γ-赖氨酸)树突表明,超支化结构是诱导球状体形成的基础,但与基于相同的超支化结构的底物上生长的那些相比,它们形成速度较慢,尺寸减小且稳定性较差通过层粘连蛋白氨基酸序列,即YIGSR,在它们的最上面的分支世代上被功能化。研究表明,纳米结构和生物识别都需要结合起来,以实现干细胞球体形成的基质,就像在成人干细胞小生境中在体内观察到的那样。与在相同的超支化结构的底物上生长的底物相比,它们的尺寸减小且稳定性较差,所述超支化结构已通过层粘连蛋白氨基酸序列即YIGSR在其最上面的分支代进行了功能化。研究表明,纳米结构和生物识别都需要结合起来,以实现干细胞球体形成的基质,就像在成人干细胞小生境中在体内观察到的那样。与在相同的超支化结构的底物上生长的底物相比,它们的尺寸减小且稳定性较差,所述超支化结构已通过层粘连蛋白氨基酸序列即YIGSR在其最上面的分支代进行了功能化。研究表明,纳米结构和生物识别都需要结合起来,以实现干细胞球体形成的基质,就像在成人干细胞小生境中在体内观察到的那样。
更新日期:2020-04-21
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