Cells for cells
MSU has developed a new material for growing stem cells
MSU Press Service
Researchers from the Institute of Regenerative Medicine of the Medical Research and Educational Center of Moscow State University have developed a new method for obtaining a framework for stem cells that can be implanted in a patient to build up his missing tissues and even organs. The framework was created with the help of mesenchymal stromal cells, from which connective tissue cells of bones, cartilage, fat, etc. are obtained. This material is better created by the classical method – from fibroblasts. The research may be useful for creating new technologies of regenerative medicine based on stem cells.
The article was published in the journal Frontiers in Cell and Developmental Biology (Novoseletskaya et al., Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potential Multipotent Stem Cell Response to Differentiation Stimuli).
Stem cells are the main tool of regenerative, regenerative medicine. They are immature, that is, they do not have a "profession": they are kidney cells, muscle cells or something else. When interacting with various molecules, they are able to divide and transform into other types of cells. This property allows you to grow tissues and even some organs from them. But at the same time, a specific framework is needed, which by itself or with ready-made cells can be implanted in the patient.
In living organisms, the role of such a 3D framework is played by the extracellular matrix. It is a network consisting mainly of collagen and fibronectin proteins. The matrix fills the entire space between the cells and serves as a mechanical support for them. In addition, many molecules are attached to the matrix, with the help of which cells coordinate their work and division. Extracellular matrix can also be used as a "smart" biomaterial for regenerative medicine, but so far there is no ideal way to obtain it and the molecular mechanisms by which it can regulate the differentiation of stem cells have not been established.
Stem cells differ in their ability to differentiate, that is, to divide into types. Some can give rise to the whole organism, others – only a small group of cells. In adults, there are three groups of them: hematopoietic, multipotent mesenchymal and tissue-specific stem cells. They differ in their location in the body and in the ways of possible specialization. The descendants of the first are blood cells, the second are connective tissue cells, and the third are responsible for restoring dead cells in certain tissues during injuries.
"Any stem cells in the body are located in a specialized environment, the so-called stem cell niche, and the extracellular matrix is its most important structural and regulatory component. It is known that mesenchymal stromal cells can synthesize it in such niches, first of all. We developed a matrix with their help, removed all the cells from it and then checked how well tissue-specific multipotent stem cells would take root on it. It turned out that they were activated, that is, they began to prepare for division and began to respond more effectively to signals that trigger their differentiation in different directions. Our results were noticeably better than in the case of the matrix developed by fibroblasts," she said Anastasia Efimenko, Candidate of Medical Sciences, Head of the Laboratory of Tissue Repair and Regeneration of the Institute of Regenerative Medicine of the Medical Research and Educational Center of Moscow State University.
To find out the mechanism of this process, the authors studied the change in the signaling cascades of the cell, that is, the ratio of molecules transmitting information "from signal to action" inside the cell. To do this, they compared the levels of proteins participating in signaling cascades in stem cells before and after growing on a matrix.
"We managed to find out that when landing on the matrix, cells were transitioning from a state of rest to a state of "combat readiness", that is, in readiness for differentiation," said Ekaterina Novoseletskaya, a graduate student of the Department of Biochemistry and Molecular Medicine at Moscow State University, the first author of the article.
At the same time, a central role in the activation of these cascades was played by special receptors to the extracellular matrix – integrins, which transmit various signals between cells. For this to happen, a molecule containing a special sequence of amino acids, for example, RGD, must attach to the integrin. This triggers a chain of reactions that leads to a change in the behavior of the cell. Integrins are also involved in regulating the differentiation of stem cells. Scientists blocked them with the help of special RGD peptides and chemical inhibitors. This made it impossible for them to interact with the matrix and transmit a signal inside the cell. At the same time, the response of cells to differentiation stimuli was greatly slowed down, which confirms the central role of RGD-binding integrins in these processes.
Biologists have been looking for ways to efficiently produce an extracellular matrix to support cells and control their behavior for a long time. The described approach will allow to get rid of the reactions of the patient's immune system to the transplant, more precisely to fragments of foreign DNA. This problem often occurs when transplanting tissues and organs from donors – they may be other people or animals. The material is cleaned at the same time, but there is still a risk. The matrix obtained by scientists was tested for the presence of molecules that could cause rejection. They have not been found, but no human studies have been conducted yet.
The cell matrix is ready for "sowing".
The approach proposed by the researchers to obtaining extracellular matrix using mesenchymal stromal cells may be in demand for the creation of new biomaterials capable of stimulating tissue regeneration by controlling the differentiation of human stem cells.
The research was supported by a grant from the Presidential Program of the Russian Science Foundation.
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