To what extent do the characteristics of stem cells determine their therapeutic capabilities

The considerable interest that currently exists in stem cells is primarily due to the prospects for their biomedical application. However, the progress of further research in this direction and, moreover, the success of clinical application depends on how well we are able to control the functions of stem cells. The most important points of this direction include, first of all, the identification of signals and the identification of conditions that contribute to the maintenance of the properties of stem cells and affect their cellular functions. Moreover, it is important to create optimal conditions for the cultivation of stem cells. 

When A.Ya. Friedenstein and his co-authors discovered stem cells in the stroma (mesenchyme) of the "adult" bone marrow in the 70s, then later there were works proving the presence of stem cells in almost all organs of adult animals and humans. However, stem cells do not exist in the body by themselves, they are located in the microenvironment, which is usually referred to by the term niche. Currently, this term is usually understood as a set of factors that ensure the viability and self-reproduction of stem cells and differentiation of daughter transient cells. The factors in question include the presence of the basement membrane, extracellular matrix molecules and the presence of neighboring cells producing growth factors and various regulatory molecules. Niches are part of the structural and functional units that make up tissues, and stem cells are firmly fixed in the niche with the help of adhesion molecules, for this purpose, in particular, a class of adhesive molecules called integrins is used. On the other hand, existing free stem cells can find their way into the appropriate niche thanks to chemotaxis, when the cell moves in a certain direction, responding to specific chemical signals. The importance of niches for stem cells is great. First of all, it concerns the restriction of stem cell proliferation, which is necessary to maintain tissue homeostasis.  On the other hand, niches provide conditions for maximum protection of stem cells from external influences. Stem cells receive signals from their microenvironment that are necessary for their self-maintenance. Intracellular signals control the ability of stem cells to unlimited proliferation, and the pluripotency of stem cells depends on the expression of transcription factors. The decoding of these signals has led to significant progress in the development of cultivation conditions that promote the differentiation of embryonic stem cells (ESCs) into specific cell types characteristic of muscle and nerve tissue, vascular structures and cardiac muscle. However, the need for a large number of combinations of growth factors and the inclusion of specific development-related gene control sometimes led to an unsuccessful attempt to obtain specific cell types from ESCs, which manifested itself in malignant transformation or the formation of teratomas.

Another important characteristic of stem cells concerns the peculiarities of their division, which should provide some kind of critical balance between two possibilities: preserving and maintaining the identity of stem cells, on the one hand, and initiating cellular differentiation, on the other. Symmetrical and asymmetric division is possible, which manifests itself differently in different types of stem cells. In the first case, the daughter cells resulting from division are no different from the mother cell, retaining all the parental characteristics. In the second case, with asymmetric division, one cell retains the characteristics of the parent stem cell, and the other acquires properties that guide it along the path of differentiation. Embryonic stem cells during early embryonic growth are characterized by symmetrical division, in which a logarithmic accumulation of cell mass occurs, and the daughter cells themselves remain totipotent. In the later stages of embryogenesis (when laying embryonic leaves) ESCs begin to divide asymmetrically. The same is true of postnatal stem cells. The molecular mechanisms of asymmetric division are not very clear.  However, studies on model objects indicate that regulatory signals come from the environment of stem cells. Before division, special proteins accumulate in place of the future differentiated daughter cell, providing asymmetric division. For example, one of the poles of an asymmetrically dividing cell can be attached to surrounding cells with the help of certain molecules. As a result, one of the daughter cells remains attached to the environment cell and retains the properties of stem cells, while the second daughter cell is not connected to the microenvironment and is able to perceive differentiation signals. Researchers from the European Laboratory of Molecular Biology in Heidelberg (Germany) have proved the existence of a direct link between defective stem cells and cancerous tumors. Scientists claim that only a few molecules are enough to cause a tumor, which appeared before the division of stem cells in the wrong place and at the wrong time. This process is also subject to viral transformation, which has been proven on teratoma cells (E.E. Zueva, 2005).

Thus, the realization of the therapeutic possibilities of stem cells directly depends on how much we are aware of the signals regulating their functioning and division and are able to manipulate them. The active introduction of stem cells into clinical practice is preceded by fundamental studies of their biology and, of course, preclinical trials.