Mechanical Mapping of Neural Stem Cell Differentiation

点击翻译按钮获取中文摘要

Neurodegenerative diseases such as Alzheimer's and Parkinson's are characterized by an irreversible loss of neurons that can lead to severe cognitive and motor deficits. These disorders generate an enormous burden on society, with healthcare costs of hundreds of billions of dollars in the U.S. alone. Current treatment options are generally not curative and can only provide temporary relief from symptoms. Stem cell therapy is an emerging technology with the potential of permanently replacing or repairing neural cells lost in neurodegenerative disorders. Improving the efficacy of stem cell therapy requires understanding of the factors that influence stem cell differentiation, the process by which stem cells generate new neurons. While most research efforts have been directed to analyzing the biochemical and genetic factors involved in the differentiation process, recent discoveries have highlighted contributions from mechanical properties of the cellular environment. This project will investigate this aspect of stem cell differentiation by employing a novel technique, Brillouin microscopy that can provide three-dimensional information on biomechanical properties of tissues at the cellular level. The objective is to determine the importance of mechanical cues in directing stem cell differentiation, and provide critical information for improving the effectiveness of regenerative therapies. This project provides an excellent opportunity to educate and train graduate students and postdoctoral researchers at the interface between engineering and life sciences. In addition to advanced students, undergraduate students enrolled in the Harvard-MIT Summer Institute for Biomedical Optics will be given the opportunity to participate.The current understanding of biomechanical properties of stem cells is mostly based on cell culture studies, showing that the mechanical parameters of the extracellular environment such as stiffness have a significant influence in directing differentiation. However, the extent to which these results represent the behavior of stem cells in brain tissues is unclear. One of the major obstacles is the lack of techniques for investigating the elastic properties of tissues with three-dimensional resolution down to the cellular and subcellular level. Brillouin imaging can bridge this gap given its non-contact nature and high spatial resolution. In this research, Brillouin imaging will be validated as a tool to provide reliable measurements of elastic modulus of neural cells and tissues. The technique will be used to map the heterogeneity of mechanical properties in the mouse brain, both at the level of the different brain structures and, in the different regions, at the cellular level to understand the origin of such spatial variations. The effect of this mechanical heterogeneity on differentiation will then be assessed by correlating the lineage of stem cells introduced into the brain with the elastic properties of the local microenvironment measured with Brillouin imaging