Republic Center for Hematology and Transfusiology

Minsk, Belarus

Republic Center for Hematology and Transfusiology

Minsk, Belarus
SEARCH FILTERS
Time filter
Source Type

Shakhbazau A.,University of Calgary | Shcharbin D.,National Academy of Sciences of Belarus | Petyovka N.,Republic Center for Hematology and Transfusiology | Goncharova N.,Republic Center for Hematology and Transfusiology | And 4 more authors.
Journal of Pharmaceutical Sciences | Year: 2012

We report the adaptation of dendrimer-based nonviral expression system for ciliary neurotrophic factor (CNTF) overproduction in human mesenchymal stem cells (hMSCs) embedded into fibrin-based three-dimensional (3D) matrix. Time-restricted neurotrophin expression enables autologous adult stem cells for additional trophic support and increases their therapeutic potential in neuroregeneration applications. Polyamidoamine (PAMAM)-NH 2 dendrimers of fourth generation effectively provided virus-free delivery and expression of CNTF-internal ribosome entry site-green fluorescent protein cassette with a transfection efficiency in hMSCs over 11%. CNTF levels in transfected cultures were 10-fold higher as compared with the control cells. Dendrimer-driven CNTF expression also persisted in hMSCs embedded into fibrin-based 3D matrix, an emerging vehicle for cell delivery or bioartificial organ formation. Nonviral modification of autologous adult stem cells with use of dendrimers is a novel tool perspective in terms of biosafety and technological availability. © 2011 Wiley Periodicals, Inc.


Shcharbin D.,National Academy of Sciences of Belarus | Dzmitruk V.,National Academy of Sciences of Belarus | Shakhbazau A.,University of Calgary | Goncharova N.,Republic Center for Hematology and Transfusiology | And 10 more authors.
Pharmaceutics | Year: 2011

Research concerning new targeting delivery systems for pharmacologically active molecules and genetic material is of great importance. The aim of the present study was to investigate the potential of fourth generation (P4) cationic phosphorus-containing dendrimers to bind fluorescent probe 8-anilino-1-naphthalenesulfonate (ANS), anti-neoplastic drug cisplatin, anti-HIV siRNA siP24 and its capability to deliver green fluorescent protein gene (pGFP) into cells. The interaction between P4 and ANS (as the model drug) was investigated. The binding constant and the number of binding centers per one molecule of P4 were determined. In addition, the dendriplex between P4 and anti-HIV siRNA siP24 was characterized using circular dichroism, fluorescence polarization and zeta-potential methods; the average hydrodynamic diameter of the dendriplex was calculated using zeta-size measurements. The efficiency of transfection of pGFP using P4 was determined in HEK293 cells and human mesenchymal stem cells, and the cytotoxicity of the P4-pGFP dendriplex was studied. Furthermore, enhancement of the toxic action of the anti-neoplastic drug cisplatin by P4 dendrimers was estimated. Based on the results, the fourth generation cationic phosphorus-containing dendrimers seem to be a good drug and gene delivery carrier candidate. © 2011 by the authors; licensee MDPI, Basel, Switzerland.


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.


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.


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.

Loading Republic Center for Hematology and Transfusiology collaborators
Loading Republic Center for Hematology and Transfusiology collaborators