Geometry turns ordinary cells into stem cells
Physical limitations cause mature connective tissue cells to fall into childhood
Kirill Stasevich, "Science and Life"
The stem cells that make up the embryo give rise to all our tissues and organs, and those stem cells that are preserved in an adult organism, although they do not have the "omnipotence" of embryonic ones, are still able to renew the wearing body for the time being.
It is clear why doctors and biologists are so actively trying to figure out cell-stem secrets: if we learned how to control such cells, we could grow organs to replace those who are ill, nip in the bud – literally – various congenital pathologies, and finally, even slow down aging.
The most promising in this sense are embryonic stem cells, which not only can divide for a very, very, very, almost indefinitely, but also have so-called pluripotency, that is, they can turn into a cell of absolutely any other type.
Until recently, "omnipotent" stem cells could only be obtained from embryos, and in this regard, researchers faced a lot of legal difficulties. But then it turned out that mature, differentiated cells, for example, connective tissue fibroblasts, can be converted into a stem state.
The role of fibroblasts is to synthesize the proteins collagen and elastin, as well as other molecules that make up connective tissue. However, it is worth adding some special proteins to fibroblasts that change the activity of genes in cells in a special way, as fibroblasts will literally turn into childhood – they will endlessly divide and they can be programmed to transform, for example, into muscle cells or skin epithelial cells. Such artificial stem cells are called induced pluripotent, and they are almost indistinguishable from embryonic stem cells.
Nevertheless, many people do not really trust artificial stem cells: they are easy to deal with in the laboratory, but there is a possibility that in a living organism they can turn into malignant, and this is due to molecular interference in the genetic kitchen. Therefore, now different researchers are looking for a way to make them the safest, how to learn how to turn mature cells into stem cells so as to minimally intrude into genetic programs. (Although it is worth noting that many biologists believe that the differences between artificial stem cells and natural ones are quite small.)
The method described in the PNAS journal by researchers from Singapore National University (Roy et al., Laterally confined growth of cells induces nuclear reprogramming in the absence of exogenous biochemical factors), does not require any explicit reprogramming at all: the authors of the work claim that mature cells can turn into stem cells themselves if they are restricted in a special way in space.
Fibroblasts were planted on a rectangular area, where they divided, grew and became rectangular themselves. But then there were even more of them, and they, climbing on top of each other, gradually formed a cellular ball. When the genetic activity of the cells in such balls was checked, it turned out that the genes that normally work in mature fibroblasts were turned off, and the genes that usually work in pluripotent stem cells were turned on. And then such cells that grew on rectangular sites were quite able to turn into cells of a different type (although some became fibroblasts again).
Fibroblasts growing in a rectangular cell form a spherical tower and gradually acquire stem abilities (illustration: National University of Singapore).
Whether such a geometric method will be effective enough to obtain safe stem cells with its help will be shown by further research (just in case, we emphasize once again that in this case everything went without adding any special molecular regulators to the cells).
However, the results obtained once again suggest that when we study the behavior of cells, it is necessary to take into account not only the biochemical signals they receive from the environment, but also the shape of this very environment – that is, the physical limitations in which cells have to exist.
According to the authors of the work, mechanical forces play an important role both during embryonic development and, say, during wound healing: in the damaged area, cells turn out to be in a different geometry, which prompts them to activate the stem program and heal the damage faster.
Here we can recall that we once wrote about the role of geometry in the life of cells - two years ago, an article appeared in the same PNAS, which said that cells, when they absorb particles from the environment, pay attention to the shape of what they eat, preferring to eat elongated and rounded.
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