Of the adult stem cells, mesenchymal stem cells (MSCs) appear to have the best potential for regenerative medicine. MSCs contain precursors that are able to differentiate into numerous types of cells but with a much lower risk of tumorigenicity. The heterogeneity of the bone marrow stem cell population makes it difficult to resolve the conflicting data on MSC plasticity. The specificity of current markers available to identify MSCs fails to separate the populations of structurally distinct cells. Hence, strategies that isolate and maintain the subpopulations of MSCs would transform the field of stem cell biology. In this work, a novel hypothesis for separating and isolating pure populations of stem cells will be tested. To test this hypothesis, investigators will use an integrative approach that couples mechanics modeling with experiments to predict the surface properties required to maintain subpopulations of MSCs. This will eventually facilitate a more uniform cell population to be established and studied for their capacity to differentiate into specific lineages, thereby enhancing their differentiation efficiency. The PI will integrate research into curriculum at Michigan State University and engage graduate, undergraduate and high school students in research in this multidisciplinary area.
Stem cells are versatile and a promising source of cells for the regeneration of aged, injured and disease tissues. Mesenchymal stem cells (MSCs), derived from bone marrow stroma, are adult stem cells (ASCs) with multipotency to differentiate into various cell lineages. Stem cells residing in tissue-specific niches contain instructions for differentiation, i.e. regenerating tissue upon injury. However, a significant hurdle before stem cells can be used clinically for tissue engineering applications lies in designing environments that trigger these desired results. A better understanding of the combined roles of internal (e.g., gene and protein levels) and external cues (e.g., biochemical factors, matrix elasticity and anisotropy) are needed in order to appropriately control them. The overall goal of this EAGER project was to enhance neural differentiation and polarity of MSCs. The findings of this study are not limited to MSCs and should be broadly applicable to other types of tissue differentiation, as well as other types of cells. Previous studies that addressed the polarity of stem cells had modified the topography of the surface to which the cells attached. We hypothesize that anisotropy, independent of the surface topography, can play a role in aligning the stem cells. Indeed we found that MSCs cultured on pre-stretched substrates align parallel to the stretched direction, without changes in surface topography. This is significant in that it suggests inherent properties of the material, namely anisotropy, in addition to its elastic properties can be capitalized upon to enhance the transdifferentiation of MSCs.
