Convert human skin cells directly into functional neurons

U.S. researchers have for the first time directly converted human skin cells into functional forebrain neurons, without the need for stem cells of any kind, according to a study published on Thursday in the online edition of journal Cell. The findings offer a new and potentially more direct way to produce replacement cell therapies for Alzheimer\'s and other neurodegenerative diseases. Such cells may prove especially useful for testing new therapeutic leads. In the 1980s and 90s, scientists realized that embryonic stem cells, because of their pluripotency (ability to develop into any kind of cell) and capacity for self-renewal, might be useful in regenerating or replacing tissue after injury or disease. However, the use of cells from human embryos raised ethical issues, triggering a search for alternatives. A breakthrough came in 2007, when researchers determined how to genetically reprogram human skin cells to become induced pluripotent stem (iPS) cells, which are similar to naturally pluripotent cells. Although this advance allowed researchers to avoid using embryonic stem cells, iPS technology remains complex, inefficient, and time-consuming. Moreover, the pluripotent stem cells by their nature are capable of forming tumors, leading to potential safety concerns. In 2010, Stanford University researchers reported turning mouse skin cells directly into neurons using transcription regulators ( proteins that switch genes on or off), bypassing the need to create iPS cells. Building on that work, Asa Abeliovich, associate professor at Columbia University Medical Center, and his team used a different combination of transcription regulators, plus several neuronal support factors, to convert human skin cells into forebrain neurons. The induced neurons appear to be the same as ordinary neurons, judging from electrophysiological testing and gene expression profiling. The researchers also showed that the neurons are able to send and receive signals in laboratory culture and when transplanted into the central nervous system of mice. These findings indicate that the induced neurons are capable of neuronal activity. \"Direct reprogramming is fundamentally different from making neurons with iPS technologies,\" says Abeliovich. \"Using direct reprogramming, you could, in theory, take someone\'s skin cells and in a couple of weeks have fully functional neurons ready for replacement cell therapy.\" \"Although the project is still at early stages and certainly not ready for clinical applications, therapies based on direct reprogramming seem more realistic than those based on iPS technology,\" says Abeliovich.