Friday, October 7, 2011

Geneticists turn liver cells into nerves

An important new step in the generation of cells from the nervous system, which we can possible use to restore functions in disabled patients. While scientists normally make use of stem cells that are consequently guided into becoming cells of choice, Stanford University used liver cells. These hepatocytes can be turned into neurons, the cells of the nervous system, with the introduction of just three genes. This seemingly simple operation brings the generation of neurons for tissue repair in disabled people one step forward.

With the introduction of the three genes to the genome of hepatocytes, it took only two to three weeks before the cells started to express typical neuron markers, while liver cell genes ceased to express. However, a small part of their liver origin remains: although the expression of genes was dramatically altered, the scientists still found marginally higher expression of liver genes, compared to true neurons.

Normally scientists use various kinds of stem cells to direct them into differentiation. Embryonic stem cells (ES) have the power to become every cell type, but their use is controversial because they are derived from embryos. However, recent studies have shown that ES can also be cloned, which allows for creation of these stem cells without having to obtain an embryo first. An alternative is reprogramming adult cells into becoming stem cells. These so-called induced pluripotent stem cells (iPS) make it possible to create stem cells without using embryos, but do retain a form of memory from the cell they used to be. Thirdly, a population called adult stem cells have the possibility to regenerate tissue, but are limited in their differentiating capabilities. They do have a stem cell character, but have already committed to a specific cellular lineage. These adult stem cells are reprogrammable, and they are often easier to obtain than iPS or ES. The downside is that when a patient is suffering from a disease, their tissue regenerating adult stem cells are often found to be damaged as well, and can even be the cause of the problem. In this case, regeneration is not possible with the patient's own cells, as they are the ones that need to be replaced.

A previous study showed it is possible to transform adult cells, without using stem cells. In these experiments, however, scientists only showed the transformation of one blood cell to another. Liver cells and neurons are more distinct from each other, which makes the cellular change much harder. Because they are from a different cellular lineage, more genes have to be shut off and on before the transformation is complete. Such dramatic alterations in cell behaviour were long thought to be impossible, which rendered stem cells as the main focus for artificial tissue creation.

Directly guiding adult cells into becoming cells of choice could prove to be an easier way to create tissue that we can use to regenerate damaged body parts in patients. Neurons, for example, are hardly repaired by the body itself, which makes it an important target for regeneration studies. With this new technique, bring artificial tissue to the patient could very well have been made easier. More research is required to elucidate whether the cells are functional, and can work together to provide functional restoration in an animal model. Using stem cells, scientists have already shown that treatment to restore funcion in the spinal cord can be succesful.

Even if this will not yield any suitable therapies, it is still an important step in learning how cells develop and differentiate. Finely controlling this process will give many possibilities for research and medicine. 

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