Human stem cells show promise against fatal children's diseases

June 4, 2008,

Scientists have used human stem cells to dramatically improve the condition of mice with a neurological condition similar to a set of diseases in children that are invariably fatal, according to an article in the June issue of the journal Cell Stem Cell.

With a one-time injection of stem cells just after birth, scientists were able to repair defective wiring throughout the brain and spinal cord – the entire central nervous system – of mutant "shiverer mice," so called because of the way they shake and wobble. The work marks an important step toward the day when stem cells become an option for the treatment of neurological diseases in people.

Neuroscientists at the University of Rochester Medical Center injected a type of fetal human stem cell known as glial stem cells into newborn mice born with a condition that normally claims their lives within about 20 weeks of birth, after a lifetime of seizures and other serious consequences. While most of the 26 mice that received transplanted glial stem cells still died, a group of six lived far beyond their usual lifespan, and four appeared to be completely cured – a first for shiverer mice. The scientists plan to gather more evidence before trying the approach in sick children.

"It's extremely exciting to think about not only treating but actually curing a disease, particularly an awful disease that affects children," said neurologist Steven Goldman, M.D., Ph.D., a leader in manipulating stem cells to treat diseases of the nervous system. "Unfortunately, right now, we can do little more for many of these conditions besides tell parents to prepare for their kids to die."

Thousands of children with rare, fatal disorders known as pediatric leukodystrophies share a central problem with the shiverer mice: Their brain cells lack sufficient myelin, a vital fatty coating that wraps around cells in the brain like insulation around an electrical wire. Myelin coats long sections, known as axons, of brain cells called neurons, and without it, the electrical signaling between neurons becomes sluggish and muddied, causing a variety of symptoms. Myelin loss is at the heart of multiple sclerosis, and also plays a role in the symptoms of diabetes, high blood pressure, and other diseases.

In children, diseases of myelin go by a host of names but share the same features: a childhood and young adulthood that may include weakness, difficulty standing or walking, seizures, dementia, paralysis, and ultimately, death. These diseases, which include Tay-Sachs, Krabbe's, Canavan's, Pelizaeus-Merzbacher, Vanishing White Matter Disease and a host of others are each rare, but collectively they kill thousands of children every year. Just last week, Lorenzo Odone, whose battle with one such disease, adrenoleukodystrophy, was featured in the film Lorenzo's Oil, passed away. Currently there is no treatment for any of these conditions.

Goldman and first author and scientist Martha Windrem have been working on shiverer mice for more than a decade. In work published in 2004 in Nature Medicine, the team restored myelin in a widespread area of an animal's brain, by injecting human stem cells that eventually become oligodendrocytes, the cells that produce myelin. In those earlier experiments, the team attempted to repair cells in only certain parts of the brain. Although the methods were effective, the treatment didn't actually improve the health of the mice.

In the latest work, the team took advantage of the routes that cells commonly take to migrate from one region of the brain to another. They injected approximately 300,000 human stem cells into the brain of each mouse, choosing five particular spots because of their ability to serve as launch pads of sorts for stem cells to migrate and colonize the entire brain and spinal cord.

And that's just what happened in some of the mice. In just two months, the glial stem cells multiplied and spread, covering nerve cells in almost the entire central nervous system, exactly mirroring their distribution in the brains of healthy mice. For several months after that, the cells produced myelin that coated nerve cells throughout the entire brain and spinal cord; from then on, the brain cells functioned normally, conducting impulses as quickly as in normal mice.

Not all of the transplanted mice fared well. Of 26 mice treated with stem cells, about three-quarters died, typically from seizures, within a couple of weeks of their untreated counterparts. But the six treated mice that lived longer recuperated to a degree hardly thought possible. The four mice that still survived one year after treatment improved rapidly, had no seizures, and were practically free of symptoms.

"We kept expecting them to die. Not only did they not die, but they improved day by day," said Goldman, who is director of the Center for Translational Neuromedicine and professor of Neurosurgery and Neurology.

The stem cells established themselves and spread throughout the brain with similar success in all the transplanted mice, including the ones that died near the time of their untreated counterparts. So why did some mice live longer? Goldman believes it was a race against time: Many of the mice were so sick that constant seizures killed them before the stem cells could take hold, propagate, spread, and remyelinate brain cells.

Source: University of Rochester

Explore further: Why get a filling when you could print a new smile?

Related Stories

Why get a filling when you could print a new smile?

February 20, 2018
Twinges. Painful teeth. About one in 10 people suffer from dental sensitivity caused by worn enamel. But rather than providing short-term solutions like special toothpastes or fillings, new techniques could print whole new ...

Stem cell vaccine immunizes lab mice against multiple cancers

February 15, 2018
Stanford University researchers report that injecting mice with inactivated induced pluripotent stem cells (iPSCs) launched a strong immune response against breast, lung, and skin cancers. The vaccine also prevented relapses ...

Induced pluripotent stem cells could serve as cancer vaccine, researchers say

February 15, 2018
Induced pluripotent stem cells, or iPS cells, are a keystone of regenerative medicine. Outside the body, they can be coaxed to become many different types of cells and tissues that can help repair damage due to trauma or ...

Researchers find adult endothelial stem cells that can make fully functional blood vessels

February 15, 2018
The proper function of blood vessels is essential to life: blood vessels are responsible for transporting oxygen-rich red blood cells, nutrients, and immune cells throughout the body, to name just a few functions. Defects ...

Team reports progress in pursuit of sickle cell cure

February 16, 2018
Scientists have successfully used gene editing to repair 20 to 40 percent of stem and progenitor cells taken from the peripheral blood of patients with sickle cell disease, according to Rice University bioengineer Gang Bao.

Lab-grown human cerebellar cells yield clues to autism

February 16, 2018
Increasing evidence has linked autism spectrum disorder (ASD) with dysfunction of the brain's cerebellum, but the details have been unclear. In a new study, researchers at Boston Children's Hospital used stem cell technology ...

Recommended for you

Fabric imbued with optical fibers helps fight skin diseases

February 23, 2018
A team of researchers with Texinov Medical Textiles in France has announced that their PHOS-ISTOS system, called the Fluxmedicare, is on track to be made commercially available later this year. The system consists of a piece ...

Low-calorie diet enhances intestinal regeneration after injury

February 22, 2018
Dramatic calorie restriction, diets reduced by 40 percent of a normal calorie total, have long been known to extend health span, the duration of disease-free aging, in animal studies, and even to extend life span in most ...

Artificial intelligence quickly and accurately diagnoses eye diseases and pneumonia

February 22, 2018
Using artificial intelligence and machine learning techniques, researchers at Shiley Eye Institute at UC San Diego Health and University of California San Diego School of Medicine, with colleagues in China, Germany and Texas, ...

Gut microbes protect against sepsis—mouse study

February 22, 2018
Sepsis occurs when the body's response to the spread of bacteria or toxins to the bloodstream damages tissues and organs. The fight against sepsis could get a helping hand from a surprising source: gut bacteria. Researchers ...

Breakthrough could lead to better drugs to tackle diabetes and obesity

February 22, 2018
Breakthrough research at Monash University has shown how different areas of major diabetes and obesity drug targets can be 'activated', guiding future drug development and better treatment of diseases.

Fertility breakthrough: New research could extend egg health with age

February 22, 2018
Women have been told for years that if they don't have children before their mid-30s, they may not be able to. But a new study from Princeton University's Coleen Murphy has identified a drug that extends egg viability in ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

sapodobrasil
not rated yet Jun 07, 2008
Very, very positive!

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.