Researchers use stem cells to create disease models

Sep 28, 2010 By David Bauman

(PhysOrg.com) -- University of Connecticut researchers have used skin cells from patients with the genetic disorders Angelman Syndrome (AS) and Prader-Willi Syndrome (PWS) to generate induced pluripotent stem (iPS) cells.

Like human embryonic stem (hES) cells, iPS cells can become any cell type in the human body, including , also known as neurons. Since both of these syndromes have , neurons were produced from the iPS cells for each of the two diseases so that the root causes could be understood and new therapies developed.

“We are generating individualized to create in vitro models of human disease,” says Marc Lalande, professor of Genetics and Developmental Biology and director of UConn’s Stem Cell Institute. “This allows us to investigate diseases such as Angelman and Prader-Willi syndromes by creating stem cells from a patient for studies in a laboratory dish. This type of information is absolutely necessary to improve our ability not only to understand and treat these two syndromes but also other human conditions with intellectual disabilities or seizures or abnormal feeding behavior.”

This study will appear the week of Sept. 27 in the early edition of the Proceedings of the National Academy of Sciences.

People with AS have profound , lack of speech, seizures, hand flapping, and motor and balance disorders. “Patients with Angelman Syndrome live full lives, which means they are in constant need of caregivers,” says Stormy Chamberlain, an assistant professor of genetics and developmental biology at the UConn Health Center.

Children with PWS suffer early postnatal feeding difficulties and poor muscle tone, but later develop an insatiable appetite and uncontrollable eating, which results in severe obesity that begins during early childhood. PWS individuals also have behavioral problems that are similar to obsessive-compulsive disorder. Due to their obsession with food, people with PWS often live in specialized group homes, where food cabinets and refrigerators are kept tightly locked.

“Prader-Willi Syndrome is a cruel disorder because in addition to the extreme food compulsion, the patients also burn fewer calories, making weight control for these individuals particularly difficult,” notes Chamberlain.

Angelman and Prader-Willi syndromes are caused by an abnormal chromosome 15. Humans typically have 23 pairs of chromosomes - one member of each pair is inherited from the mother, while the other member is inherited from the father, to convey hereditary traits that parents pass to their offspring.

Lalande discovered more than 20 years ago that cells keep track of which parent passes on each chromosome 15. PWS occurs when an abnormal copy of chromosome 15 is inherited from the father, while AS is caused by an abnormal chromosome 15 inherited from the mother.

“We know that the patients’ skin cells remember which chromosome 15 was inherited from the father and which one was inherited from the mother, but we didn’t know whether this memory would be erased upon reprogramming the skin cells as stem cells,” says Chamberlain, who leads the research team that generated the new stem cell lines. “We were surprised to find that the stem cells remember from which parent they were inherited perfectly!”

This was surprising because the process of reprogramming skin cells involves erasure of the cell’s memory of being a skin cell and resetting it to the memory of a stem cell. If the memory of parental origin of chromosome 15 were erased, it would mean that the iPS cells could not be used to make working stem cell models of the two syndromes.

To generate the iPS cell lines, the UConn research team inserted a cocktail of genes into taken from the patients to trigger a process that reprogrammed the skin cell to an embryonic-like or pluripotent state and then coaxed them into becoming neurons.

“With live neurons in a dish, we can study what is wrong with the cells that make up the brains of kids with these disorders,” Chamberlain says. “The ultimate goal, is to take the neurons, figure out what’s wrong with them, and develop drugs that can fix that defect.”

Chamberlain speculates that Angelman and Prader-Willi syndromes are not likely to be repaired by cell replacement therapy, like some other disease: ”In our case we think that the stem cell-derived neurons can be better used to study the disease and design drugs for these disorders.”

Explore further: Microbes provide insights into evolution of human language

Related Stories

Using Stem Cells to Study Alcohol Dependence

Apr 12, 2010

(PhysOrg.com) -- An estimated 14 million Americans - one in eight - are addicted to alcohol or will develop an alcohol use disorder. Yet despite the very high personal and economic costs, the vast majority ...

Researchers Reprogram Human Induced Pluripotent Stem Cells

Jan 27, 2009

For the first time, UCLA researchers have reprogrammed human induced pluripotent stem (iPS) cells into the cells that eventually become eggs and sperm, possibly opening the door for new treatments for infertility using patient-specific ...

Recommended for you

Cell division speed influences gene architecture

20 hours ago

Speed-reading is a technique used to read quickly. It involves visual searching for clues to meaning and skipping non-essential words and/ or sentences. Similarly to humans, biological systems are sometimes ...

Secret life of cells revealed with new technique

22 hours ago

(Phys.org) —A new technique that allows researchers to conduct experiments more rapidly and accurately is giving insights into the workings of proteins important in heart and muscle diseases.

In the 'slime jungle' height matters

23 hours ago

(Phys.org) —In communities of microbes, akin to 'slime jungles', cells evolve not just to grow faster than their rivals but also to push themselves to the surface of colonies where they gain the best access ...

Queuing theory helps physicist understand protein recycling

Apr 22, 2014

We've all waited in line and most of us have gotten stuck in a check-out line longer than we would like. For Will Mather, assistant professor of physics and an instructor with the College of Science's Integrated Science Curriculum, ...

User comments : 0

More news stories

When things get glassy, molecules go fractal

Colorful church windows, beads on a necklace and many of our favorite plastics share something in common—they all belong to a state of matter known as glasses. School children learn the difference between ...

FCC to propose pay-for-priority Internet standards

The Federal Communications Commission is set to propose new open Internet rules that would allow content companies to pay for faster delivery over the so-called "last mile" connection to people's homes.

SK Hynix posts Q1 surge in net profit

South Korea's SK Hynix Inc said Thursday its first-quarter net profit surged nearly 350 percent from the previous year on a spike in sales of PC memory chips.