Bypassing stem cells, scientists make neurons directly from human skin

Aug 04, 2011

Researchers have come up with a recipe for making functional neurons directly from human skin cells, including those taken from patients with Alzheimer's disease. The new method may offer a critical short cut for generating neurons for replacement therapies of the future, according to research published in the August 5th issue of the journal Cell, a Cell Press publication. Already, the converted neurons are beginning to yield insights into what goes wrong in the Alzheimer's brain and how diseased neurons might respond to treatment.

In earlier approaches to generate neurons from skin cells, those adult cells first had to be returned to an embryonic stem cell state. Those cells, called induced pluripotent stem (iPS) cells, are hard to come by – less than one percent of cells are typically reprogrammed successfully. In addition, the entire process is time-consuming, requiring months to coax cells into iPS cells and then stimulate them to become neurons.

"iPS cells are exciting given the limits on cloning and embryonic stem cells, but it is still a roundabout and lengthy process if the goal is to take patient cells or normal cells and use them as replacement cells," said Asa Abeliovich of Columbia University, senior author of this study.

Not only are there efficiency issues, there is also an increasing concern about the stability of iPS cells, he said. Their ability to grow and produce any cell type makes them a cancer risk. Moreover, the cells may have limited use as models for understanding disease states because the processes used to derive them "may erase or overwhelm" the natural biology of the cells.

To get around these potential pitfalls, Abeliovich's team started with known transcriptional regulators and, through a process of trial and error, identified a cocktail of factors that could turn human skin cells into neurons. While the process was not initially very efficient, they refined the protocol, ultimately converting about 50 percent of the cells.

"It is a huge leap over the iPS-based process," he said. It is also more efficient than a similar method recently developed by another group.

When studied in a dish, the neurons derived from healthy skin cells could fire and receive signals, just like normal neurons. What's more, when placed into the brains of developing mice, the converted cells were able to connect up to the existing circuitry. "They really are neurons," Abeliovich said.

The method can also produce neurons from the skin cells of patients with a rare familial form of Alzheimer's disease (AD). The AD neurons superficially looked normal, but upon closer inspection, Abeliovich's team saw abnormalities in the processing of amyloid precursor protein, the source for the amyloid plaques that riddle the brains of those with Alzheimer's disease. The neurons also showed more general differences in the way proteins inside the cell move around.

Abeliovich says that to really understand what goes wrong in Alzheimer's disease it will be important to look at what is happening in living human neurons. Earlier studies have been limited to exploring the consequences of the Alzheimer's mutations in tumor cells, skin cells or in mouse models of the disease.

Potentially the most exciting use of these Alzheimer's neurons will be for testing new drug candidates. Abeliovich notes that when the cells were treated with one existing candidate drug that reduces beta amyloid production, the protein 'trafficking' problem actually worsened, raising caution about that particular treatment. Going forward, his group plans to study derived from from patients with the more common, sporadic forms of Alzheimer's disease.

"Sporadic disease accounts for 99 percent of cases and no one really knows if it is similar or different from the simpler genetic forms," Abeliovich said. "It's not a done deal that we'll be able to come up with answers, but at least we can now ask the question. In that sense, this is the tip of the iceberg."

Explore further: For cells, internal stress leads to unique shapes

Related Stories

Researchers generate functional neurons from somatic cells

Feb 24, 2009

In a new study, researchers were able to generate functionally mature motor neurons from induced pluripotent stem (iPS) cells, which are engineered from adult somatic cells and can differentiate into most other cell types. ...

Scientists produce neurons from human skin

Feb 22, 2007

Scientists from Université Laval’s Faculty of Medicine have succeeded in producing neurons in vitro using stem cells extracted from adult human skin. This is the first time such an advanced state of nerve cell differentiation ...

Skin cells could help discover cause of Parkinson's disease

Jul 14, 2010

Researchers are applying new stem cell technology to use skin samples to grow the brain cells thought to be responsible for the onset of Parkinson's disease, the UK National Stem Cell Network (UKNSCN) annual science meeting ...

Recommended for you

For cells, internal stress leads to unique shapes

1 hour ago

From far away, the top of a leaf looks like one seamless surface; however, up close, that smooth exterior is actually made up of a patchwork of cells in a variety of shapes and sizes. Interested in how these ...

Adventurous bacteria

3 hours ago

To reproduce or to conquer the world? Surprisingly, bacteria also face this problem. Theoretical biophysicists at Ludwig-Maximilians-Universitaet (LMU) in Munich have now shown how these organisms should ...

Revealing camouflaged bacteria

5 hours ago

A research team at the Biozentrum of the University of Basel has discovered an protein family that plays a central role in the fight against the bacterial pathogen Salmonella within the cells. The so cal ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

Avitar
not rated yet Aug 05, 2011
We need to get these gentlemen more research money. This is a national security issue with United States aging population.

More news stories

Chimpanzees prefer firm, stable beds

Chimpanzees may select a certain type of wood, Ugandan Ironwood, over other options for its firm, stable, and resilient properties to make their bed, according to a study published April 16, 2014 in the open-access ...

For cells, internal stress leads to unique shapes

From far away, the top of a leaf looks like one seamless surface; however, up close, that smooth exterior is actually made up of a patchwork of cells in a variety of shapes and sizes. Interested in how these ...

Down's chromosome cause genome-wide disruption

The extra copy of Chromosome 21 that causes Down's syndrome throws a spanner into the workings of all the other chromosomes as well, said a study published Wednesday that surprised its authors.

IBM posts lower 1Q earnings amid hardware slump

IBM's first-quarter earnings fell and revenue came in below Wall Street's expectations amid an ongoing decline in its hardware business, one that was exasperated by weaker demand in China and emerging markets.