Mesenchymal Stem Cells and the Synthetic Microenvironment: An Integrated Approach

该奖项的研究目标是使用微加工，活细胞成像以及遗传和分子工具来研究细胞微环境对人类间充质干细胞（hMSCs）成骨（或骨）分化的物理影响。hMSCs的成骨分化对周围细胞微环境的机械性能（如基质硬度）敏感。在这个项目中，我们将使用微加工来建立一个新的弹性微柱阵列库，通过调节这些微柱阵列的几何因子，我们可以精确地改变微柱阵列的刚度，从而改变位于微柱上的hMSCs的固有收缩或机械状态。我们建议使用这些弹性微柱阵列与不同的遗传和分子工具相结合，以研究基质刚度和细胞内细胞骨架收缩性之间的功能串扰hMSCs和他们的关键参与mechanosresponsible hMSC成骨。hMSCs是成人干细胞，形成和愈合几乎所有的机械组织在人类，包括骨。因此，理解hMSC成骨的机械调节可以提供对hMSC生物学的见解，并进一步改善hMSC体外成骨用于再生治疗。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。在此奖项的背景下开发的技术将被用作在密歇根州安阿伯和伊普西兰蒂学区的K-12学生和其他代表性不足的女性和少数民族学生的外联活动的工具。外展活动将向K-12学生揭示科学和工程方面令人兴奋的挑战及其与我们社会的密切相关性，从而激励他们追求科学和工程课程。

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.