Mesenchymal Stem Cells and the Synthetic Microenvironment: An Integrated Approach

间充质干细胞和合成微环境：一种综合方法

• 批准号: 1129611
• 负责人: Jianping Fu
• 金额: $ 37.5万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1129611&HistoricalAwards=false
• 关键词: Mesenchymal; Stem; Cells; Synthetic; Microenvironment

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.

该奖项的研究目标是利用微加工、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力学特性（如基质刚度）很敏感。在这个项目中，我们将使用微加工技术建立一个新的弹性体微柱阵列库，通过调节这些微柱阵列的几何因素，我们可以精确地改变微柱阵列的刚度，从而改变微柱上的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结合不同的遗传和分子工具来研究基质刚度和hMSCs细胞内细胞骨架收缩性之间的功能串扰，以及它们在机械反应性hMSC成骨中的重要作用。骨髓间充质干细胞是一种成体干细胞，可以形成并治愈人体几乎所有的机械组织，包括骨骼。因此，了解hMSC成骨的机械调节可能为hMSC生物学提供见解，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。在该奖项的背景下开发的技术将用于密歇根州安娜堡和伊普斯兰蒂学区的K-12学生和其他代表性不足的女性和少数民族学生的推广活动。外展活动将向K-12学生揭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。