Scientists have managed to convert human skin cells into functional neurons without having to use any kind of stem cells, researchers from Columbia University Medical Center reported in the journal Cell. This breakthrough could offer effective treatments to replace the cells of patients with Alzheimer’s disease, and other neurodegenerative illnesses.

The method, known as direct reprogramming, generated neurons from the skin cells of individuals with early-onset (familial) Alzheimer’s disease.

Study leader, Asa Abeliovich, MD, PhD, said that the induced neurons differed significantly from those made from healthy volunteers, providing a better understanding of how the disease develops.

About 25 years ago, researchers realized that embryonic stem cells could be useful in replacing or regenerating tissue after disease and injury. Embryonic stem cells can develop into any kind of cell – they are pluripotent. However, human embryo research triggered ethical debates, so researchers started looking for alternatives.

In 2007 scientists found out how to genetically reprogram human skin cells so that they would become iPS (pluripotent stem) cells – these are similar to cells which are naturally pluripotent. Even so, iPS technology continued to be inefficient, time-consuming, and complex. Pluripotent stem cells can also form tumors.

In 2010, the skin cells of mice were turned directly into neurons using proteins that switch genes on/off (transcription regulators), resulting in no more need to create iPS cells. This was done at Stanford University.

Dr. Abeliovich and team built on that work. They used a different combination of transcription regulators, as well as many neuronal support factors, to convert human skin cells into forebrain neurons. These induced neurons are apparently the same as ordinary ones, the scientists say – after electrophysiological testing and gene expression profiling.

They showed that these neurons can receive and send signals in lab culture when transplanted into the CNS (central nervous system) of mice. The authors believe that the induced neurons are capable of neuronal activity.

Dr. Abeliovich said:

“Direct reprogramming is fundamentally different from making neurons with iPS technologies. 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. What is particularly exciting is that direct reprogramming is broadly applicable to the study and treatment of a host of neurological diseases.”

The scientists then compared skin-cell-derived neurons of healthy volunteers with those from patients with familial Alzheimer’s disease.

The authors wrote:

“The latter cells (from the Alzheimer’s patients) exhibited altered processing and localization of amyloid precursor protein (APP) and increased concentration of amyloid beta, a component of APP (Alzheimer’s is thought to develop when abnormal amounts of amyloid beta accumulate in the brain, eventually killing neurons.) APP was found to collect in the cells’ endosomes, cellular compartments that sort molecules for degradation or recycling. These findings suggest that this form of Alzheimer’s is caused, at least in part, by abnormal endosomal function.”

Written by Christian Nordqvist