Stem cells are exquisitely sensitive to substrate rigidity. Hydrogel maintain stem cell properties and enable drug screening

 

2. Adult Stem Cells


The lab has developed methods to capitalize on the stem cells already present in certain adult tissues. The lab developed a flow cytometry to isolate muscle stem cells and methods for monitoring their function in vivo using a highly sensitive non-invasive bioluminescence imaging assay.


A major impediment to the use of these cells therapeutically, is that their stem cell properties, like many tissue-specific adult stem cells, are rapidly lost on tissue culture plastic. We reasoned that the cells might be sensitive to the rigidity of the substrate, and produced hydrogels with five orders of magnitude less rigidity than plastic. On this soft material, which is comparable to muscle tissue, the stem cells self-renewed and their stem cell capacity to regenerate damaged tissues was maintained, as shown upon transplantation into injured mouse muscles. 

Building on these findings, we are working to understand how cells perceive and respond to the stiffness of the material on which they are plated (signaling networks induced) and is screening for drugs that in conjunction with hydrogel culture could increase the numbers (expansion) of muscle stem cells critical to clinical applications. The combined action of biophysical and biochemical cues is key, as neither alone suffices.

Additionally, the lab is elucidating novel stem cell niche proteins and the mechanisms that maintain stemness in the body. A major goal is the discovery of therapeutic agents capable of rejuvenating the stem cell population in injured muscles of aged individuals in order to increase the quality of life.

* Sacco et al. Nature, 2008. (PDF)

* Lutolf et al., Nature, 2009.

* Gilbert et al., Science, 2010. (PDF)