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明胶微球的掺入诱导人间质干细胞球体微环境的变硬。

Stiffening of human mesenchymal stem cell spheroid microenvironments induced by incorporation of gelatin microparticles.

机构信息

The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, 313 Ferst Drive, Atlanta, GA 30332, USA.

出版信息

J Mech Behav Biomed Mater. 2012 Jul;11:63-71. doi: 10.1016/j.jmbbm.2012.02.018. Epub 2012 Mar 3.

DOI:10.1016/j.jmbbm.2012.02.018
PMID:22658155
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3528787/
Abstract

Culturing multipotent adult mesenchymal stem cells as 3D aggregates augments their differentiation potential and paracrine activity. One caveat of stem cell spheroids, though, can be the limited diffusional transport barriers posed by the inherent 3D structure of the multicellular aggregates. In order to circumvent such limitations, polymeric microparticles have been incorporated into stem cell aggregates as a means to locally control the biochemical and physical properties of the 3D microenvironment. However, the introduction of biomaterials to the 3D stem cell microenvironment could alter the mechanical forces sensed by cells within aggregates, which in turn could impact various cell behaviors and overall spheroid mechanics. Therefore, the objective of this study was to determine the acute effects of biomaterial incorporation within mesenchymal stem cell spheroids on aggregate structure and mechanical properties. The results of this study demonstrate that although gelatin microparticle incorporation results in similar multi-cellular organization within human mesenchymal stem cell spheroids, the introduction of gelatin materials significantly impacts spheroid mechanical properties. The marked differences in spheroid mechanics induced by microparticle incorporation may hold major implications for in vitro directed differentiation strategies and offer a novel route to engineer the mechanical properties of tissue constructs ex vivo.

摘要

培养多能成体间充质干细胞作为 3D 聚集体可增强其分化潜能和旁分泌活性。然而,干细胞球体的一个缺点是,多细胞聚集体固有的 3D 结构会造成有限的扩散传输障碍。为了规避这些限制,已将聚合物微球纳入干细胞聚集体中,作为局部控制 3D 微环境生化和物理特性的手段。然而,生物材料引入 3D 干细胞微环境可能会改变聚集体内细胞感知的机械力,进而影响各种细胞行为和整体球体力学。因此,本研究的目的是确定生物材料在间充质干细胞球体中的掺入对聚集体结构和机械性能的急性影响。本研究的结果表明,尽管明胶微球的掺入导致人骨髓间充质干细胞球体中出现类似的多细胞组织,但明胶材料的引入显著影响球体的机械性能。微球掺入引起的球体力学的显著差异可能对体外定向分化策略具有重要意义,并为体外工程组织构建的机械性能提供了新途径。

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