Mesenchymal Stem Cells and the Synthetic Microenvironment: An Integrated Approach

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

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.