Gene delivery to stem cells: nanoparticles instead of viral vectors?
Researchers at the Massachusetts Institute of Technology, working under the leadership of Daniel Anderson, using nanoparticles increased the ability of stem cells to stimulate the restoration of damaged vascular tissue and reduce the degree of degeneration of muscle tissue in mice. The results of the work were published on October 5 in the on-line version of the Proceedings of the National Academy of Sciences in the article "Genetic engineering of human stem cells for enhanced angiogenesis using biodegradable polymeric nanoparticles".
Scientists studying the role of stem cells in stimulating the formation of new blood vessels have suggested that after implantation into a living organism, cells may lose the ability to effectively renew tissue and maintain its viability for a long time. This issue can be solved by introducing genes into the genome of cells that enhance their functions. Usually viral vectors are used to transport genes inside cells, but the authors decided to choose a more suitable DNA delivery system.
They introduced nanoparticles into the culture medium of mouse bone marrow stem cells, which include biodegradable positively charged polymers capable of binding DNA molecules and delivering them inside cells. In the experiment, the gene of vascular endothelial growth factor (VEGF), a signaling molecule that stimulates the growth of new blood vessels, was attached to the nanoparticles. Modified stem cells were injected into eight mice in the damaged areas. The authors claim that the cell membrane captures nanoparticles, which, once in the intracellular space, release the DNA attached to them. However, they note that the exact mechanism of this process is still unclear.
Two weeks later, scientists found that the density of blood vessels around the damaged area of tissue in animals that received injections of cells modified with nanoparticles was twice as high as in mice that were injected with cells that did not contain an additional gene or modified with conventional carrier molecules. Four weeks after the injection, the modified cells continued to stimulate the growth of new blood vessels, while reducing the degree of degeneration of muscle tissue.
Regenerative Biology Specialist from California State University (San Francisco) Arnold Kriegstein, who was not involved in the study, believes that the positive effects of using nanoparticles in this case may be temporary. He notes that among the results of the work there is an observation according to which the level of VEGF in the muscle tissue of mice significantly increased two days after the introduction of modified cells, but again sharply decreased four days after the procedure.
Kriegstein suggests that using an adenovirus vector to deliver a growth factor gene to cells makes more sense than using nanoparticles. Despite the existing doubts about the safety of using viral vectors, such a campaign can give longer and more pronounced results than the use of nanoparticles.
The authors of the work do not deny the advantages of the method of gene transfer using viral vectors, however, they argue that the use of nanoparticles is much safer and, after a certain improvement in the approach, has great potential not only in cellular medicine, but also in the treatment of oncological and hereditary diseases.
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of The Scientist: Nanoparticles spur stem cells?
19.10.2009