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利用生物物理线索实现人骨髓间充质干细胞在几何图案内的双重分化

Exploiting the Biophysical Cues toward Dual Differentiation of hMSC's within Geometrical Patterns.

作者信息

Joshi Akshay, Kaur Tejinder, Singh Neetu

机构信息

Centre for Biomedical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India.

Biomedical Engineering Unit, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.

出版信息

Langmuir. 2023 May 16;39(19):6691-6697. doi: 10.1021/acs.langmuir.3c00070. Epub 2023 May 2.

DOI:10.1021/acs.langmuir.3c00070
PMID:37129583
Abstract

A wide variety of cues from the extracellular matrix (ECM) have been known to affect the differentiation of stem cells . In particular, the biophysical cues and cell shape have been known to affect the stem cell function, yet very little is known about the interplay between how these cues control differentiation. For the first time, by using photolithography to pattern poly(ethylene glycol) (PEG), patterns of square and triangular geometries were created, and the effect of these structures and the biophysical cues arising were utilized to differentiate cells into multiple lineages inside a same pattern without the use of any adhered protein or growth factors. The data from these studies showed that the cells present at the edges were well elongated, exhibit high aspect ratios, and differentiated into osteogenic lineage, whereas the cells present at the center exhibit lower aspect ratio and were primarily adipogenic lineage regardless of the geometry. This was correlated to the higher expression of focal adhesion proteins at the edges, the expression of which have been known to affect the osteogenic differentiation. By showing MSC lineage commitment relationships due to physical signals, this study highlights the importance of these cues and cell shape in further understanding stem cell behavior for tissue engineering applications.

摘要

已知细胞外基质(ECM)中的多种信号会影响干细胞的分化。特别是,生物物理信号和细胞形状已知会影响干细胞功能,但对于这些信号如何控制分化之间的相互作用却知之甚少。首次通过使用光刻技术对聚乙二醇(PEG)进行图案化,创建了方形和三角形几何形状的图案,并利用这些结构以及由此产生的生物物理信号,在不使用任何粘附蛋白或生长因子的情况下,将细胞在同一图案内分化为多个谱系。这些研究的数据表明,边缘处的细胞伸长良好,具有高纵横比,并分化为成骨谱系,而无论几何形状如何,中心处的细胞纵横比更低,主要为脂肪生成谱系。这与边缘处粘着斑蛋白的较高表达相关,已知该蛋白的表达会影响成骨分化。通过展示由于物理信号导致的间充质干细胞谱系定向关系,本研究突出了这些信号和细胞形状在进一步理解用于组织工程应用的干细胞行为方面的重要性。

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