Current approaches to the genetic modification of mesenchymal stromal cells to increase their therapeutic efficacy

Abstract

One of the extensively developing innovative approaches to the treatment of socially significant diseases is the use of cell technologies based on the transplantation and co-transplantation of mesenchymal stromal cells (MSCs) or on the use of their secretome components. The interest in these cell therapies is driven by the low immunogenicity of MSCs, relative simplicity of the cell isolation and handling, a wide range of therapeutic effects and proven efficacy of reparative and immunosuppressive action thereof. By now, more than 2,000 clinical trials on the use of MSCs or their products in various pathological conditions have been completed, with more than 200 in the last five years. Both the immunosuppressive and the regenerative effects of MSCs are mediated to a great extent by their secretome which includes chemokines, growth factors, non-coding RNAs, and other active molecules. At the same time, the degree and character of MSCs effects depend not only on the microenvironment or body state, but also on the characteristics of MSCs themselves, including the genetic determinants governing levels of synthesis of bioactive molecules. In this review, we consider options of genetic modification of MSCs in order to increase their therapeutic efficacy.