Nanotechnology for neuroregeneration

M.Kh.Salakhov, N.I.Silkin, V.D.Skirda, G.A.Fomina, Yu.A.Chelyshev, V.G.Shtyrlin

Russia

 

To improve results of the treatment of posttraumatic and postischemic dysfunction of the nervous system is an actual problem in medicine. Results available up to now are extremely unsatisfactory and do not correspond to the present quality of life. Neurotrauma is accompanied by the destruction of neurons, degeneration of axons, disbalance of communications in the neuronal networks and functions they control. The bioengineering approach seems to be the most promising one to prevent the secondary degeneration and to maintain the growth of nerve fibers. It assumes the application of genetic and cell technologies and the creation of an adequate replacing matrix. The latter also serves as a carrier of cells, bioactive substances, pharmacological neuroprotectors and stimulators of the axon growth. To combine these approaches in a single bioengineering complex promises an essential increase in the efficiency of posttraumatic neuroregeneration.

The improvement of standards of treatment of posttraumatic and postischemic neurologic disorders in many respects is connected with the development and introduction of cellular technologies. In this direction the intensive studies of the transplantation of cells of a wide spectrum are carried out. Among them, the most promising are embryonic stem cells, neural stem cells and lineage-restricted precursors for neurons and glia from various sources, olfactory ensheathing cells, bone marrow stromal cells, Schwann cells, etc. Cellular transplantations reduce the secondary degeneration of neurons, stimulate the regeneration of axons and remyelination. To increase the efficiency of the cellular transplantation in order to stimulate neuroregeneration, the cells are genetically modified to enhance the production and delivery in the injured tissue-target of neurotrophic factors, growth factors, adhesion molecules, antiapoptotic molecules, cell fate determinants and other stimulators of axonal growth. Transfection ex vivo is carried out in various ways. The delivery of nucleic acids in cells with the use of the vector systems being the basis of genotherapy is considered to be a promising method of the treatment of neurological deficit and is actively developed with respect to the problem of neuroregeneration. Viral particles used as vectors for the transfection of cells are characterized by high transfection activity, but their practical application is limited by their potential pathogenicity and high immunogenicity.

Non-viral ways of the gene transfection are based on the application of chemical or physical methods of the delivery. Among them are the direct injection of pure DNA\plasmid, electroporation and application cationic liposomes. Non-viral vectors on the basis of cationic polymers due to their high cytotoxicity and low efficiency of transfection are considered to be less promising. Therefore, an actual problem of the transport of genes into cells is to search for new non-viral vectors. The application of functional nanosystems is one of the priority approaches to solving this problem. Supramolecular systems on the basis of fullerenes and carbon nanotubes, having a highly organized nanostructure and a large surface area, are promising enough in this respect. Calixarenes carrying positively charged radicals for the linkage with DNA transported by a molecule, which are elaborated in the KSU, may serve as an essentially new platform for the non-viral gene delivery. The visualization of immune nanoparticles and relevant tagged transplanted cells by magnetic resonance tomography and immunohistochemical methods is already widely used in experiments on neurotransplantation. These experiments are of the obvious clinical importance for the establishment of survival, extension and topography of the migration ways of transplanted cells.