Scientists accelerate aging in stem cells to study age-related diseases like Parkinson's

December 5, 2013
These are images of nerve cells under i) control conditions without PD and without progerin; ii) with progerin but no PD. iii) with both progerin and PD. Credit: Cell Stem Cell, Miller et al.

Stem cells hold promise for understanding and treating neurodegenerative diseases, but so far they have failed to accurately model disorders that occur late in life. A study published by Cell Press December 5th in the journal Cell Stem Cell has revealed a new method for converting induced pluripotent stem cells (iPSCs) into nerve cells that recapitulate features associated with aging as well as Parkinson's disease. The simple approach, which involves exposing iPSC-derived cells to a protein associated with premature aging called progerin, could enable scientists to use stem cells to model a range of late-onset disorders, opening new avenues for preventing and treating these devastating diseases.

"With current techniques, we would typically have to grow pluripotent stem cell-derived cells for 60 or more years in order to model a late-onset disease," says senior study author Lorenz Studer of the Sloan-Kettering Institute for Cancer Research. "Now, with progerin-induced aging, we can accelerate this process down to a period of a few days or weeks. This should greatly simplify the study of many late-onset diseases that are of such great burden to our aging society."

Modeling a specific patient's disease in a dish is possible with iPSC approaches, which involve taking from patients and reprogramming them to embryonic-like stem cells capable of turning into other disease-relevant cell types like neurons or . But iPSC-derived cells are immature and often take months to become functional, similar to the slow development of the human embryo. As a result of this slow maturation process, iPSC-derived cells are too young to model diseases that emerge late in life.

To overcome this hurdle, Studer and his team exposed iPSC-derived skin cells and neurons, originating from both young and old donors, to progerin. After short-term exposure to this protein, these cells showed age-associated markers that are normally present in old cells.

This is an intracellular aggregate in PD neuron -- a feature only seen in PD neuron treated with progerin. Credit: Cell Stem Cell, Miller et al.

The researchers then used iPSC technology to reprogram skin cells taken from patients with Parkinson's disease and converted the into the type of neuron that is defective in these patients. After exposure to progerin, these neurons recapitulated disease-related features, including neuronal degeneration and cell death as well as mitochondrial defects.

"We could observe novel disease-related phenotypes that could not be modeled in previous efforts of studying Parkinson's disease in a dish," says first author Justine Miller of the Sloan-Kettering Institute for Cancer Research. "We hope that the strategy will enable mechanistic studies that could explain why a disease is late-onset. We also think that it could enable a more relevant screening platform to develop new drugs that treat late-onset diseases and prevent degeneration."

Explore further: New study explains why promising dementia drugs failed in clinical trials

More information: Cell Stem Cell, Miller et al.: "Human iPSC-based Modeling of Late-Onset Disease via Progerin-induced Aging." dx.doi.org/10.1016/j.stem.2013.11.006

Related Stories

New study explains why promising dementia drugs failed in clinical trials

December 5, 2013
Alzheimer's disease is the most common cause of dementia among older people, yet there currently are no effective drugs to stop, slow or prevent disease progression. A study online December 5th in the ISSCR's journal Stem ...

Researchers model familial amyloidosis in vitro using iPSC technology

October 31, 2013
Researchers from Boston University School of Medicine (BUSM) and Boston Medical Center (BMC) have generated the first known disease-specific induced pluripotent stem cell (iPSC) lines from a patient with familial transthyretin ...

Generating dopamine via cell therapy for Parkinson's disease

July 2, 2012
In Parkinson's disease, the loss of dopamine-producing cells in the midbrain causes well-characterized motor symptoms. Though embryonic stem cells could potentially be used to replace dopaminergic (DA) neurons in Parkinson's ...

Recommended for you

A sodium surprise: Engineers find unexpected result during cardiac research

July 20, 2017
Irregular heartbeat—or arrhythmia—can have sudden and often fatal consequences. A biomedical engineering team at Washington University in St. Louis examining molecular behavior in cardiac tissue recently made a surprising ...

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.