ИСТИНА

Human adult multipotent mesenchymal stromal cells (MSC) were in a spotlight of potential therapeutic application throughout the last decade. Discovery of their paracrine activity and use of secretome for “cell therapy without cells” have remained a hot topic in the field. We summarize and report our extensive development in the field using adeno‐associated virus, baculovirus and plasmid DNA vectors to express growth factors in MSC with a goal to enrich their secretome and thus functionalize for higher therapeutic efficacy. Besides using gene modification for MSC secretome functionalization we addressed the issue of cell delivery and used cell sheet (CS) technology to facilitate cell survival in models of human disease of ischemic nature. Eventually, our studies of MSC application lead us to a conclusion that we may try to apply cell secretome alone and we used a basic approach expressing human BDNF and uPA by pDNA transfection to producent cells and obtained samples enriched by a neurotrophic growth factors. We evaluated its efficacy and observed increased animal survival, reduction of neurological disorders and brain injury volume in a model of intracerebral hemorrhage in rats. We suggest a number of directions for future development in the field and believe that in regenerative medicine MSC gene modification are a great option taking into account their paracrine mode of action in human disease. The study was supported by RSF grant #19‐75‐30007; State assignment and Development Program of the Interdisciplinary Scientific and Educational School of Lomonosov Moscow State University “Molecular technologies of the living systems and synthetic biology.”