Nerve stem cells of the 999th sample
A pure population of nerve stem cells promises significant progress in the treatment of nervous diseases
LifeSciencesToday based on the materials of the University of Rochester Medical Center:
Stem Cell Advance a Step Forward for Treatment of Brain DiseasesAmerican scientists have developed an unprecedented accurate method of isolating nerve stem cells from human nervous tissue, giving rise to all types of brain cells.
This is an important step towards the development of new treatments for diseases of the nervous system, such as Parkinson's and Huntington's diseases, and spinal cord injuries.
The work of neurologists at the University of Rochester Medical Center is published in the Journal of Neuroscience. The group of researchers was led by the head of the Department of Neurology, Doctor of Medicine and Philosophy Steven Goldman (Steven Goldman).
The article (Prospective Identification, Isolation, and Profiling of a Telomerase-Expressing Subpopulation of Human Neural Stem Cells, using sox2 Enhancer-Directed Fluorescence-Activated Cell Sorting) is the result of six years of efforts by the Goldman group to develop a more advanced method for isolating pure nerve stem cell preparations directly from human brain tissue. Neural stem cells have the ability to renew and differentiate into a number of types of brain cells – for example, oligodendrocytes, which can help people with multiple sclerosis, or neuron, necessary for patients with Parkinson's disease. By the end of the first few months of human embryonic development, there are very few neural stem cells, and it is a big problem for scientists to find and isolate them. Nevertheless, if stem cells can become a method of treating a number of diseases of the nervous system, it is simply necessary to look for ways to solve this problem.
Until now, most attempts to isolate human embryonic stem cells have involved culturing brain tissue in a laboratory tissue culture for several months. In addition, today's technologies do not allow only stem cells to be isolated; usually, progenitor cells similar to stem cells (progenitor cells) that have already entered the path of differentiation into a certain type of cell are also captured. The difference between these types of cells is of great importance for scientists who often prefer to work only with non-simulated nerve stem cells, both in the treatment of brain diseases requiring the replacement of many types of cells, and in the study of their functions.
The new method developed in Goldman's laboratory allows obtaining only stem nerve cells, and directly from brain tissue. The new technology saves months of time and lab work and gives scientists a clearer picture than ever before of exactly how stem cells function in the brain.
Several surprises awaited Goldman and his colleagues during their research. As expected, certain classes of genes encoding proteins active in mouse neural stem cells – such as members of the Notch and WNT families – were indeed extremely active. But upon closer examination, the scientists found that the newly isolated neural stem cells expressed several genes from the same families, which were previously virtually unknown in humans, and which had never been involved in the functions of the human brain. At the same time, some genes that are active and important in the stem nerve cells of mice did not have such significance in human cells.
"Although studies on mice and other animals serve as good models, ultimately, in order to really understand human diseases, it is necessary to study human tissue and the human body," warns Goldman, who is also one of the directors of the Rochester Center for Translational Neuromedicine. "Although the common signaling pathways active in both mice and humans are very similar, individual genes are different. This is something that cannot be predicted. Our work is a good demonstration that studies on mice cannot give a complete picture of what types of therapies should be used in the treatment of humans."
The new method is based on a segment of DNA encoding the Sox2 protein, which has long been recognized as a key gene of stem cells. Since the gene is active only in stem cells, the key to the problem is finding and isolating cells with the active Sox2 gene.
To track this gene, the scientists identified a DNA sequence known as an enhancer, which determines whether the Sox2 gene is active in neural stem cells. They linked this section of DNA to a gene that causes cells to emit light of a certain wavelength, and then packaged the resulting synthetic DNA into a virus. The virus was used to deliver synthetic DNA to the cells of a sample of brain tissue. Nerve stem cells – and only they – began to emit light of a certain color, which, in turn, allowed only these cells to be identified and isolated from the tissue culture. As a result, the researchers obtained a pure population of human neural stem cells – the first population of these cells with such a degree of purity.
The possibility of obtaining human stem cells more efficiently should help the development of treatment methods based on their transplantation. In recent years, several studies have been initiated using human neural stem cells on children with incurable diseases of the nervous system known as leukodystrophy. But this field is still in its infancy, and Goldman hopes that the cell types currently used will soon be replaced by more efficient stem and progenitor cells.
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09.12.2010