Genetic Modification of Mesenchymal Stem Cells for Neurological Disease Therapy: What Effects Does it Have on Phenotype/
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Genetic Modification of Mesenchymal Stem Cells for Neurological Disease Therapy: What Effects Does it Have on Phenotype/Cell Behavior, Determining Their Effectiveness? Nour Ebrahim1 · Victoria James2 · Albert A. Rizvanov1 · Yana Mukhamedshina1,3,4
© Springer Nature Switzerland AG 2020
Abstract Mesenchymal stem cells are a promising tool in regenerative medicine, and their functions can be enhanced through genetic modification. Recent advances in genetic engineering provide several methods that enable gene delivery to mesenchymal stem cells. However, it remains to be decided whether genetic modification of mesenchymal stem cells by vectors carrying reporter or therapeutic genes leads to adverse effects on morphology, phenotypic profiles, and viability of transplanted cells. In this regard, we focus on the description of genetic modification methods of mesenchymal stem cells, their effectiveness, and the impact on phenotype/cell behavior/proliferation and the differentiation ability of these cells in vitro and in vivo. Furthermore, we compare the main effects of genetically modified mesenchymal stem cells with native mesenchymal stem cells when applied in the therapy of neurological diseases. Key Points The choice of method to obtain genetically modified mesen‑ chymal stem cells (MSCs) does not only affect the level and duration of expression of recombinant genes, but can also affect the phenotype and behavior of the transduced cells. Genetic modification of MSCs can improve the therapeutic properties of MSCs in the ischemic and traumatic injury of the central nervous system by improving neurological func‑ tion, reducing lesion volume, and modulating glial activation. Transplantation of genetically modified MSCs leads to a longer overall lifespan, better induction of local trophic effects, and attenuation of neuronal injury in neurode‑ generative diseases compared with native MSCs. * Yana Mukhamedshina yana.k‑z‑[email protected] 1
Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russian Federation
2
School of Veterinary Medicine and Science, University of Nottingham, Nottingham, UK
3
M.M. Shemyakin-Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russian Federation
4
Kazan State Medical University, Kazan, Russian Federation
1 Introduction The use of cells as medicinal products has become a rev‑ olutionary field in medicine, featuring a wide range of applications. Stem cells can be obtained from both adult or embryonic tissue, but it is also possible to genetically modify cells for at least two purposes: (1) reprogramming different mature cells into stem cells through the introduc‑ tion of key transcription factors, giving rise to induced pluripotent stem cells [1] and (2) enhancing expression of therapeutic genes encoding trophic factors [2]. For the latter purpose, mesenchymal stem cells (MSCs) are being increasingly used, considering their unique properties such as extensive proliferation in
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