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Shakhbazau A.V.,National Academy of Sciences of Belarus | Kosmacheva S.M.,Republic Center for Hematology and Transfusiology | Kartel N.A.,National Academy of Sciences of Belarus | Potapnev M.P.,Republic Center for Hematology and Transfusiology
Cell and Tissue Biology | Year: 2010

In addition to traditional osteogenic, chondrogenic, and adipogenic differentiation, mesenchymal stem cells are considered to be capable of also giving rise to neural lineage. We overview the transgenic approach for the neurogenic differentiation of MSCs, including the expression of neurotrophic factors, signaling molecules, and other transgenes with neurogenic properties. © 2010 Pleiades Publishing, Ltd. Source

Shakhbazau A.,University of Calgary | Shcharbin D.,National Academy of Sciences of Belarus | Bryszewska M.,University of Lodz | Kumar R.,University of Calgary | And 7 more authors.
Current Medicinal Chemistry | Year: 2012

Genetic engineering of stem cells and their derivatives has the potential to enhance their regenerative capabilities. Here, dendrimer-and lipofection-based approaches were used for non-viral neurotrophin-3 (NT-3) over-expression in Schwann cells differentiated from skin precursors (SKP-SCs). A variety of dendrimers were first tested for transfection efficiency on HEK 293T cells, with PAMAMNH2 G4 found most effective and used subsequently for SKP-SCs transfection. Plasmid-based expression resulted in increased NT-3 release from SKP-SCs in both adherent and microcarrier-based culture. In a proof-of-concept study, the microcarrier/SKP-SCs were implanted into the injured nerve, and transfected cells were shown to detach, integrate into the nerve tissue and associate with regenerating axons. Virus-free systems for transient neurotrophin expression are a feasible and biologically safe option to increase the therapeutic value of stem cells and stem cell-derived cells in nerve repair strategies. Further work to develop bioprocesses for expansion of SKP-SCs on microcarriers in bioreactors is still needed. © 2012 Bentham Science Publishers. Source

Shakhbazau A.,University of Calgary | Shcharbin D.,National Academy of Sciences of Belarus | Seviaryn I.,Republic Center for Hematology and Transfusiology | Goncharova N.,Republic Center for Hematology and Transfusiology | And 6 more authors.
Molecular Pharmaceutics | Year: 2012

This study reports the use of a nonviral expression system based on polyamidoamine dendrimers for time-restricted neurotrophin overproduction in mesenchymal stem cells and skin precursor-derived Schwann cells. The dendrimers were used to deliver plasmids for brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3) expression in both rodent and human stem cells, and the timelines of expression were studied. We have found that, despite the fact that transfection efficiencies and protein expression levels were comparable, dendrimer-driven expression in human mesenchymal stem cells was characterized by a more rapid decline compared to rodent cells. Transient expression systems can be beneficial for some neurotrophins, which were earlier reported to cause unwanted side effects in virus-based long-term expression models. Nonviral neurotrophin expression is a biologically safe and accessible alternative to increase the therapeutic potential of autologous adult stem cells and stem cell-derived functional differentiated cells. © 2012 American Chemical Society. Source

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