The stiffness of stem cells
Sara Cassidy, Ph.D.
Induced pluripotent stem cells (iPSCs) are a man-made type of stem cell. They are generated by reprogramming a mature cell — called a terminally differentiated cell — back to a cell that resembles a stem cell from an embryo and is able to differentiate and mature into a variety of different cells and tissues. The conditions needed to revert adult cells into stem cells were first discovered in 2006 at Kyoto University. Since then, iPSCs have been intensely studied to better understand the molecular mechanisms that allow for the return to a stem-like state, and for good reason. iPSCs eliminate the ethical concerns related to studying embryonic stems cells (ESCs), and they hold much promise for regenerative and personalized medicine. For example, iPSCs derived from a patient with amyotrophic lateral sclerosis (ALS) were directed to differentiate into motor neurons (the cells destroyed during ALS) and iPSCs have been reported safe for use in treating macular degeneration (although efficacy is still being worked out). iPSCs can be made from easily accessible cell sources, like skin cells from a patient, so they are present in nearly inexhaustible numbers, and they carry significantly reduced risk of rejection compared to cells derived from other people or sources.
Many gene expression changes accompany the reversion of adult cells to iPSCs. And recent evidence using mouse cells suggests they also undergo biophysical changes. Urbanska et al. characterized the physical attributes of single neural progenitor cells induced to become iPSCs and then allowed to re-differentiate along a neural lineage. They found that as adult cells become iPSCs, they become stiffer and this stiffness was similar to measurements of mouse ESCs. In the reverse direction, as iPSCs differentiate to neuronal cells they become more pliable.
These data have interesting implications for use of iPSCs for future treatment. For instance, cell stiffness could be used to identify and enrich for iPSCs in mixed cell populations, which is less invasive than other methods (i.e. fluorescently labeling proteins only present in pluripotent cells) that jeopardize cell viability. Future studies will hopefully identify the source of the stiffness, whether it be changes in the cytoskeleton or cell membrane, and investigate the functional implications of these changes.
Sara Cassidy, Ph.D., is a senior scientific writer at the Jackson Laboratory for Genomic Medicine.