Mesenchymal Stem Cells and the Synthetic Microenvironment: An Integrated Approach

该奖项的研究目标是使用微制造、活细胞成像以及遗传和分子工具来研究细胞微环境对人骨髓间充质干细胞(HMSCs)成骨(或骨)分化的物理影响。人骨髓间充质干细胞的成骨分化对周围细胞微环境的力学性质(如基质硬度)非常敏感。在这个项目中，我们将利用微加工技术建立一种新型的弹性微柱阵列库，通过调节微柱阵列的几何因素，我们可以精确地改变微柱阵列的硬度，从而改变躺在微柱上的人骨髓间充质干细胞的固有收缩或机械状态。我们建议使用这些弹性微柱阵列结合不同的遗传和分子工具来研究hMSCs的基质硬度和细胞内细胞骨架收缩之间的功能串扰，以及它们在机械反应性hMSC成骨中的关键作用。hMSCs是成体干细胞，可以形成和修复几乎所有的人类机械组织，包括骨。因此，了解hMSC成骨的力学机制，有助于深入了解hMSC的生物学特性，进一步提高hMSC的体外成骨能力，为再生治疗提供理论依据。该奖项的教育活动将对不同教育水平、性别和种族的学生产生广泛影响。在该奖项范围内开发的技术将被用作向密歇根、安娜堡和伊普西兰蒂学区的K-12学生以及其他代表性不足的女性和少数族裔学生开展外联活动的工具。外展活动将向K-12年级的学生展示科学和工程领域令人兴奋的挑战及其与我们社会的密切联系，从而激励他们学习科学和工程课程。

The research objective of this award is to use microfabrication, live cell imaging, and genetic and molecular tools to investigate the physical effects of the cell microenvironment on the osteogenic (or bone) differentiation of human mesenchymal stem cells (hMSCs). The osteogenic differentiation of hMSCs is sensitive to the mechanical properties (such as matrix stiffness) of the surrounding cellular microenvironment. In this project, we will use microfabrication to establish a novel library of elastomeric micropost arrays, where by modulating the geometrical factors of these micropost arrays, we can precisely change the stiffness of the micropost array and thus the innate contractile or mechanical state of hMSCs lying on the microposts. We propose to use these elastomeric micropost arrays coupled with different genetic and molecular tools to investigate the functional crosstalk between substrate stiffness and intracellular cytoskeletal contractility of hMSCs and their crucial involvements in the mechanoresponsive hMSC osteogenesis.hMSCs are adult stem cells that form and heal nearly all of the mechanical tissues in humans, including bone. Thus, understanding the mechanical regulation of hMSC osteogenesis may provide insights into hMSC biology and further improve hMSC osteogenesis in vitro for regenerative therapeutics. The educational activities of this award will have broad impacts on students from different educational levels and genders and ethnicities. The technologies developed in the context of this award will be used as vehicles for outreach activities to K-12 students and other underrepresented female and minority students in the Michigan Ann Arbor and Ypsilanti school districts. The outreach activities will reveal to K-12 students the exciting challenges in science and engineering and their close relevance to our society, thus motivating them to pursue science and engineering curricula.