CAREER: Biomechanical Regulation of Mesenchymal Stem Cell Differentiation

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This Faculty Early Career Development Program (CAREER) award will support research to study the how mesenchymal stem cell differentiation is regulated. Mesenchymal stem cells have self-renewal properties. These cells have great potential in cell-based therapies for tissue engineering and regenerative medicine. However, the fundamental mechanisms of how mesenchymal stem cells differentiate into cells that make formation remains poorly understood. This project will systematically study the interactions of biophysical and biochemical factors that affect differentiation. This work will use a novel micro-engineered platform to identify the functions and mechanisms that influence mesenchymal stem cell differentiation. The educational activities will provide a goal-oriented, project-based, hands-on learning experience to a broad audience, with an emphasis on women and underrepresented minorities. Undergraduate and graduate students will be trained through project-based courses and research opportunities. In addition, summer outreach activities will increase teachers' awareness of STEM careers and enhance the engagement of K-12 students into STEM education. By improving the fundamental understanding of mesenchymal stem cell differentiation, this project will support the development of biomanufacturing and tissue engineering systems to produce specific stem cell lineage that are necessary for normal organ function. The specific research goal of this project is to identify the function and mechanisms of mechanosensitive non-coding RNAs in regulating osteogenic differentiation. The overarching focus is to investigate how stiffness, geometric guidance, and traction force regulate non-coding RNAs during mesenchymal stem cell differentiation, using a novel multiplex nanobiosensor, 2D and 3D culture systems. This will be accomplished through three research objectives. The first objective is to develop and characterize a novel multiplex nanobiosensor for non-coding RNAs detection at the single cell level. The second objective is to elucidate the mechanosensitive role of non-coding RNAs and their crosstalk with biophysical factors at the tissue, cell, and molecular level. The final objective is to investigate the mechanoregulation of non-coding RNAs during osteogenic differentiation in 3D microenvironments. Completion of this project will provide novel information and insights regarding the mechanisms underlying non-coding RNAs in response to biophysical factors. The knowledge gained from these experiments will provide new insights into the fundamental principles of mechanoregulation of osteogenic differentiation for the application of cell-based therapies, which will support the advancement of the biomanufacturing and tissue engineering systems.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.