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Direct Transformation of Adult Stem Cells to Neural Progenitors
The use of stem cells for treating injuries and disease has many potential complications. Stem cells, whether embryonic, adult, or induced, could potentially turn into any cell in the body. If this occurs after transplantation into a patient, the consequences could be severe. A central nervous system injury, for example, might end up with muscle cells growing around, reducing the likelihood that the injury could be repaired in the future. In addition, due to their highly proliferative nature, stem cells could potentially cause the development of cancerous tumors.

Stem cells transplants from adult cells have a major advantage over embryonic stem cells. A patient could act as a self donor to procure adult stem cells or induced pluripotent stem cells, thereby negating any possible transplant rejection. Embryonic stem cells cannot be obtained directly from the patient, and could possibly be rejected by the recipient. In addition, preparation of stem cells requires a great deal of work and expertise. Embryonic stem cells must be obtained by the destruction of an embryo, which may be ethically questionable. Adult stem cells are mostly obtained from bone marrow, and produce blood cell precursors. These blood cells are not appropriate for treating many disorders outside of the circulatory system. Induced pluripotent stem cells are derived from normal adult cells, which must be reverted to a more embryonic like state. Once they have been reverted, the cells must then be matured into the desired cell type, and expanded in tissue culture.

Researchers from the University of Wisconsin at Madison recently found a method to directly convert normal adult skin cells from both monkeys and humans into neural progenitor cells, without requiring a pluripotent stem cell intermediate. The neural progenitor cells that were produced are able to mature into a variety of neural cells, and can propagate easily in tissue culture as well as the host. A major advantage to this method is that fewer steps are required to develop the desired cell type. In addition, a patient could donate his or her own cells for the procedure, reducing the risk of transplant rejection. The researchers exposed the adult skin cells in culture to a virus called Sendai virus. Sendai virus is advantageous over other viral vectors used during cell reprogramming, because the genetic information of the virus does not become a permanent part of the cell. This is a safer approach than the use of other viral vectors, which have been linked to tumor formation in previous studies.

After the adult skin cells were treated with virus for twenty four hours, the culture was exposed to moderate heat. The heat was sufficient to kill the virus, but not the cells. This is another advantage to procedure, as no live virus is present when the cells are injected into the patient. The researchers were able to isolate neural progenitor cells, which can further mature and differentiate into nerve cells. The neural progenitor cells proliferate easily in culture as well as in the body. Because they have already begun the process of maturation, there is no risk of the cells turning into different tissue types once injected into a patient. The neural progenitor cells were then injected into newborn mice, and proliferated as normal. There were no apparent defects from the neural progenitor cells, such as tumor formation or the production of unwanted tissues.

Any advances made that help develop cells that can be used to therapeutic purposes are always welcome. However, like many other methods of producing neural cells, this method has some drawbacks. Using a virus to induce cellular reprogramming is always worrisome. The body’s cells have special methods to fight viral infection. Even skin cells can produce an innate response that would decrease cellular replication and turn off certain parts of the cells protein making machinery. This helps prevent the virus from growing in the host. The skin cells are able to produce certain proteins that can cause effects on other nearby cells, and may lead to inflammation. This immune response by the cells may actually prove problematic in large scale production of neural progenitors. In addition, if the virus is not sufficiently killed before the cells have been injected into the patient, this could cause serious consequences. Many patients requiring transplants are given immune-suppressant drugs, leaving them at high risk for complications due to infection. Finding the right balance between destroying the virus without harming the newly developed cells will be important before this treatment can be utilized in humans.

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Direct Transformation of Adult Stem Cells to Neural Progenitors - by bridgettpayseur - 05-06-2013, 06:38 AM
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