Physical stimuli help to transfer cells to a pluripotent state
Researchers from the University of California at Berkeley, working under the leadership of Professor Song Li, have demonstrated that during the transformation of mature cells into pluripotent cells, some chemical factors can be replaced by physical stimuli.
Scientists cultured fibroblasts isolated from human and mouse skin for 2 weeks on smooth surfaces and surfaces with parallel grooves 10 micrometers wide and 3 micrometers deep. Compounds promoting cell reprogramming were added to the culture medium. However, it did not contain low molecular weight compounds used to stimulate changes in the cell epigenome, such as valproic acid.
At the end of the experiment, it turned out that the presence of grooves on the cultivation surface increased the yield of pluripotent cells by 4 times, the properties of which are close to those of embryonic stem cells. Growing cells on frames of parallel nanofibers provided a similar result.
The currently used method of reprogramming adult cells into a pluripotent state involves the introduction of a viral vector carrying a certain set of genes into them and exposure to a combination of chemical compounds.
According to the authors, both genetic and chemical effects can have an unforeseen long-term effect on the cell. For example, one of the chemical agents used – valproic acid – is the ability to make significant changes in the epigenome of the cell, which is fraught with various, previously unpredictable, changes. Therefore, any ways to improve the process of cell reprogramming are extremely important.
Earlier studies have shown that physical and mechanical influences can influence the fate of a cell, but their effects on its epigenetic status were unclear. The results obtained by the authors indicate that the cultivation surface covered with micro-grooves improves the quality and reproducibility of the reprogramming process no worse than valproic acid.
Currently, researchers are improving the proposed technique, as well as studying the possibilities of using physical influences to reprogram pluripotent cells into cells of certain types, for example, neurons.
In pictures of Song Li's Lab (UC Berkeley) on the left are induced pluripotent stem cells derived from adult skin cells that differentiate into neurons. The cell nuclei are colored blue, and the filament protein expressed by neurons is red.
On the left – the same iPSCs differentiate into myocytes. The cell nuclei are colored blue, and the muscle fiber protein actin is green.
Article by Timothy L. Downing et al. The Biophysical regulation of epigenetic state and cell reprogramming is published in the journal Nature Materials.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of UC Berkeley:
Physical cues help mature cells revert into embryonic-like stem cells.
23.10.2013