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Human skin cells converted directly into functional neurons

Date:
August 4, 2011
Source:
Columbia University Medical Center
Summary:
Researchers have directly converted human skin cells into functional forebrain neurons, without the need for stem cells of any kind. 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.

Columbia University Medical Center researchers have for the first time directly converted human skin cells into functional forebrain neurons, without the need for stem cells of any kind. 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. The study was published in the August 4 online issue of the journal Cell.

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In another first, the researchers used this method -- called direct reprogramming -- to generate neurons from skin cells of patients with familial (early-onset) Alzheimer's disease. The induced neurons were found to differ significantly from those made from healthy individuals, providing new insights into the development of the disease, reports study leader Asa Abeliovich, MD, PhD, associate professor of pathology & cell biology and neurology in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Medical Center (CUMC).

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, Dr. Abeliovich 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 Dr. 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. "What is particularly exciting," says Dr. Abeliovich, "is that direct reprogramming is broadly applicable to the study and treatment of a host of neurological diseases."

In the second part of the study, Dr. Abeliovich compared neurons made from skin cells of healthy individuals with neurons made from patients with early-onset Alzheimer's disease. The latter cells 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, the researchers report.

Dr. Abeliovich's paper is entitled, "Directed Conversion Of Alzheimer's Disease Patient Skin Fibroblasts Into Functional Neurons." His coauthors are Liang Qiang, Ryousuke Fujita, Toru Yamashita, Herve Rhinn, David Rhee, Claudia Doege, Lily Chau, and William B. Vanti at CUMC and Sergio Angulo and Herman Moreno at the State University of New York Downstate Medical Center, Brooklyn, N.Y.

The New York State Stem Cell Science (NYSTEM), among others, provided funding for the study.



Story Source:

The above story is based on materials provided by Columbia University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Liang Qiang, Ryousuke Fujita, Toru Yamashita, Sergio Angulo, Herve Rhinn, David Rhee, Claudia Doege, Lily Chau, Laetitia Aubry, William B. Vanti et al. Directed Conversion Of Alzheimer's Disease Patient Skin Fibroblasts Into Functional Neurons. Cell, 5 August 2011; 146(3) pp. 359 - 371 DOI: 10.1016/j.cell.2011.07.007

Cite This Page:

Columbia University Medical Center. "Human skin cells converted directly into functional neurons." ScienceDaily. ScienceDaily, 4 August 2011. <www.sciencedaily.com/releases/2011/08/110804123909.htm>.
Columbia University Medical Center. (2011, August 4). Human skin cells converted directly into functional neurons. ScienceDaily. Retrieved November 22, 2014 from www.sciencedaily.com/releases/2011/08/110804123909.htm
Columbia University Medical Center. "Human skin cells converted directly into functional neurons." ScienceDaily. www.sciencedaily.com/releases/2011/08/110804123909.htm (accessed November 22, 2014).

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Bypassing Stem Cells, Scientists Make Neurons Directly from Human Skin

Aug. 4, 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 ... read more

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