05 February 2010

Retinal photoreceptors from skin cells

Scientists at Washington State University (Seattle), working under the leadership of Thomas Reh, transformed adult human skin cells into photoreceptors – light-sensitive retinal cells. When transplanted into the mouse retina, such photoreceptors were fully integrated into the surrounding tissue. (The picture shows a green photosensitive cell obtained from an adult skin cell, between the red-stained retinal cells.) The authors believe that the technique they developed will eventually form the basis of new methods of treating retinal diseases, such as retinitis pigmentosa and macular degeneration, leading to vision impairment and blindness.

First, the researchers, according to the standard protocol for creating induced pluripotent stem cells, activated several genes in skin cells, which led to the return of their characteristic ability for embryonic cells to differentiate into cells of various types. After that, they applied a previously developed technique for differentiating pluripotent cells into photoreceptors. Initially, this technique was developed by the authors to work with embryonic stem cells, but the use of induced pluripotent cells is more preferable for regenerative medicine. The patient's skin is a ready source of cells, the use of which for transplantation completely eliminates not only ethical issues, but also problems associated with immune reactions of transplant rejection.

The photosensitive cells created by the researchers also open up new opportunities for studying currently inadequate animal models of degenerative retinal diseases, as well as for identifying new therapeutic targets for their treatment. Retinitis pigmentosa, for example, is a hereditary disease characterized by the death of photoreceptors. The DNA of photoreceptors obtained from the patient's skin cells will contain all the mutations involved in the development of the disease. This will allow researchers to identify the molecular mechanisms underlying cell death. They can also use cells to screen for molecules capable of slowing or preventing photoreceptor death.

Before the use of laboratory–grown photoreceptors in clinical practice, scientists have yet to solve a number of serious problems, first of all, to learn how to correct mutations that disrupt the normal functioning of photoreceptors using gene therapy methods. In addition, it is necessary to develop an approach that would ensure the effective engraftment of a large number of cells in the recipient's retina. The number of photoreceptors that could be implanted into the retina of mice during experiments is not enough to restore vision.

The authors note that the effective restoration of the functioning of the retina requires the integration of at least 10,000 cells into it. In the near future, researchers plan to assess the functioning of photoreceptors integrated into the retina.

The results of the work were published on January 20 in the online version of the journal PLoS ONE in the article "Generation, Purification and Transplantation of Photoreceptors Derived from Human Induced Pluripotent Stem Cells".

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of TechnologyReview: Crafting Light-Sensing Cells from Human Skin.

05.02.2010

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