Human stem cells can remember whether researchers grew them on a soft bed of polyethylene glycol or on a stiff floor of polystyrene. This mechanical memory in turn influences the fate of these stem cells, such as whether they start differentiating into fat or bone cells.
That’s one take-home message of a presentation given last week by University of Colorado, Boulder, materials scientist Kristi S. Anseth at the American Chemical Society meeting in Dallas. The work, which Anseth described to the Division of Biochemical Technology, is also the subject of a recent report in Nature Materials (2014, DOI: 10.1038/nmat3889).
Stem cell researchers already attempt to control differentiation by carefully selecting the chemical constituents in their stem cell growth media. The new results suggest that they should also consider the physical constraints of this growing environment, Anseth and her colleagues argue.
“Just as you would dose stem cells with chemical factors over time to direct differentiation, researchers should add the properties of the mechanical environment to their laboratory repertoire,” commented Wilhelm T. S. Huck, who studies cellular growth conditions at Radboud University, Nijmegen, the Netherlands.
Researchers previously had evidence that stem cells grow best in environments mimicking the stiffness or softness of their natural niche, Huck said. But he added, “Nobody had studied whether cells could shake the memory of their past environments.”
Anseth’s team studied human mesenchymal stem cells, one of three major groups of human stem cells. They found two proteins, called YAP and TAZ, that can modulate the cells’ mechanical memory. Both can activate gene transcription.
When the stem cells are cultured on stiff beds, these proteins relocate from the cytoplasm to the nucleus. If the stem cells spend just a few days on stiff or soft beds, the future impact of this mechanical history is not set in stone. But spending 10 days on a particular bed leads to irreversible future differentiation of the stem cells into stiff-environment-loving bone or soft-loving fat cells.
“I think this study will prompt many groups to consider with greater care the importance of their culture conditions,” commented Dennis E. Discher, who studies stem cell culture conditions at the University of Pennsylvania.