CAREER: Understanding the Effects of Mechanical Dosing on Mesenchymal Stem Cell Identity

This Faculty Early Career Development (CAREER) grant will study how the “identity” of stem cells can be preserved by the mechanical properties of the materials that surround them. Stem cell identity is defined by their ability to divide, adapt, and differentiate. This work will focus on mesenchymal stem cells, which are adult stem cells typically sourced from bone marrow and expanded with tissue culture techniques. Controlling mesenchymal stem cell identity is important for cell manufacturing and regenerative medicine. The research goal of this project is to overcome current limitations in the cell culture environment of mesenchymal stem cells by developing materials with independently controllable properties of stiffness, adhesion, and cell-cell signaling. The educational goal of this project is to integrate research with ongoing educational activities to increase scientific literacy and equity. The work will involve programs for underrepresented high school and undergraduate students to conduct in-person summer research and attend virtual interactive modules designed to instill a passion for cell biology and materials science. The central hypothesis of this research is that mechanical dosing strategies can be leveraged to control mesenchymal stem cell proliferation, adaptation to dynamic materials, and differentiation within 3D hydrogels. This hypothesis will be tested by: (i) determining the significance of matrix mechanosensing during in vitro expansion on mesenchymal stem cell proliferation and stemness, (ii) elucidating the role of adhesive and cell-cell mimetic peptides on mesenchymal stem cell mechanical adaptation, and (iii) identifying mechanical dosing parameters that increase the differentiation potential of mesenchymal stem cells in 3D injectable hydrogels. The fundamental knowledge gained from these studies is expected to lead to a paradigm shift in current mesenchymal stem cell culture environments and result in significant advances in cell manufacturing, stem cell mechanobiology, and regenerative medicine. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.