Cell Stiffness as an Indicator of Stem Cell State and its Applications to High-Throughput Purification

Advisor
Todd Sulchek, PhD
 
Committee
Wilbur Lam, MD, PhD
Todd McDevitt, PhD
John McDonald, PhD
Paula Vertino, PhD (Emory University)

Mesenchymal and embryonic stem cells hold great potential in tissue engineering and patient-specific cell therapy, but the lack of phenotype-specific molecular markers hinders purification of target cell types for safe and efficient therapeutic technologies.  Cancer stem cells, a rare subset of tumor cells that may be responsible for tumor relapse after chemotherapy, are difficult to purify for biological characterization and future chemotherapeutic improvement.  Utilization of cell mechanical properties may represent a novel approach to identify and purify target cells, such as mesenchymal or embryonic stem cell-derived cells or cancer stem cells, even though appropriate phenotypic biomarkers are not well established.
 
Although it has been established that cellular stiffness can change as a stem cell differentiates, the precise relationship between cell mechanics and other phenotypic properties remains unclear.  Single-cell analysis will be employed to determine how changes in cell stiffness correlate with changes in molecular biomarkers during differentiation.  Secondly, microfluidic technology will be utilized to enrich target cell types based on their mechanical properties.  Revelation of additional differentiation indicators, such as cell stiffness, can improve identification and collection of starting cell populations, with applications to stem cell-based therapies and tissue engineering.