The present invention is related to the methods for improving stemness by controlling the expressions of mortalin proteins in the differentiation mechanism stage of mesenchymal stem cells. Using mesenchymal stem cells for cytotherapy inevitably requires mass production through long-term in vitro cultures. Due to the subculture that is repeated in this process, the unique properties of the stem cells are lost, and at the same time the properties change and arrive at senescence, resulting in a loss of stemness. Furthermore, cell proliferation through culture is always subject to threats from bacterial contamination, xenogeneic risk, and cellular transformation, which can affect the potency of mesenchymal stem cells. As such, many limits must be overcome for mesenchymal stem cells that have been separated from the donor to be used for cell therapy. Accordingly, the present invention uses the mechanism of the USP18-mortaline route to not only suppress the senescence of cells but also to increase the growth and survival of cells, enabling large quantities of mesenchymal stem cells to be cultured.
Stem cells are very useful and valuable because they can be used in many ways, such as in the discovery of novel drug candidates, the verification of the safety of drugs, and the exploration of efficient drugs. Mesenchymal stem cells, in particular, require cell culture for clinical application so that a large quantity of cells can be acquired, and as such the development of ideal stem cell medicine requires research regarding the differentiation mechanism that takes into consideration the unique properties of cell differentiation functions according to minute changes in the environment. The present invention provides a method to control the stemness of mesenchymal stem cells, and it enables the stable supply of stem cells by maintaining the stemness of stem cells as available for cell therapy. It is expected to play an important role in the development or research of cell medicine using converging technology of the Fourth Industrial Revolution.