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Biologists have studied how stem cells decide who to become
Scientists from Lomonosov Moscow State University, the Pavlov Institute of Physiology and the Institute of Gene Biology of the Russian Academy of Sciences have found out that a layer of stem cells is a kind of "patch" for tissue healing without scars, is very heterogeneous in its structure. Dense islets spontaneously form in it, where cells differentiate into bone and cartilage more efficiently than their more sparse "brethren". Such independence and the underlying molecular mechanisms are also characteristic of stem cells that form connective tissues in the fetus in the womb. Article on the work supported by the grant Published in the journal Biomedicines (Nimiritsky et al., Self-Organization Provides Cell Fate Commitment in MSC Sheet Condensed Areas via ROCK-Dependent Mechanism). The press service of the foundation briefly reported on the results of the study.
Regeneration is one of the most important protective functions of any living system. It allows not only to heal wounds or grow whole limbs, but also provides a constant renewal of body tissues. In multicellular cells, this function is supported by stem cells of different types that can transform (differentiate) into specialized cells of one or more tissues.
Differentiation of MMSCs into bone, cartilage and fat: monolayer and cellular layer.
Multipotent mesenchymal stromal cells (MMSCs) play an important role in the processes of renewal and restoration, which give rise to connective tissues — fat, bones and cartilage. MMSCs were found in almost all organs, and some of them enter the damaged areas with blood flow from the bone marrow, "attracted" by specific signaling molecules. There they differentiate, replacing dead cells. One of the tasks of regenerative medicine is to understand how the fate of MMSC is determined. Especially interesting is the phenomenon of their self-organization, which consists in the fact that even under minimal conditions for life, these cells independently form an ordered tissue-like structure, but it is not completely clear exactly how this happens.
"We decided to study the mechanism of self—organization of multipotent mesenchymal stromal cells, which underlies the construction of the stroma - the connective tissue component of any organ. Stroma is not just an inert "framework": interaction with it contributes to the survival, division, differentiation and migration of stem and specialized organ cells. In combination with other molecular factors secreted by the surrounding tissue, the stroma can influence the further fate of cells in the damaged area. As a rule, during healing, a connective tissue scar is formed, deprived of the function of this organ. However, if we understand how MMSCs determine which type of cells to turn into, then we can get closer to deciphering the mechanism of complete regeneration," said Pavel Makarevich, one of the authors of the study, head of the laboratory of Gene cell Therapy at the Faculty of Fundamental Medicine of Lomonosov Moscow State University.
The authors of the work conducted experiments on the MMSC line from human adipose tissue. For the study, a well-known cellular model of primary connective tissue based on a layer was used, which can also be used as a "patch" for damage to various organs. The resulting layers were grown in an environment with substances that promote the transformation of stem cells into bone, cartilage or fat. The authors observed the structures that formed the cells and evaluated the differentiation of MMSCs by specific staining.
On all media in the cell layers, areas of high cell density were formed, in which specialization was more active in the direction of dense connective tissues — bone and cartilage tissue were formed, but not fat. It turned out that in these islands, the activity of those genes that are key to the formation of dense connective tissues is sharply increased in the cells. At the same time, they suppressed the formation of proteins that promote the conversion of stromal cells into fat. Similar processes are also involved in the formation of connective tissue in the fetus.
"To some extent, this is a new look at a well-studied structure in the form of a cellular layer from MMSC — everyone perceives it as a "patch" of cells, but even in this primitive structure we found the division of culture into groups with different properties. We are trying to look at the tasks of regenerative medicine from the perspective of developmental biology and are looking for parallels between the processes that determine the formation of tissue in embryogenesis and how adult stem cells behave. This approach is very promising for the restoration of lost tissues; in the future, perhaps, we will be able to heal wounds without scars," Pavel Makarevich added.
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