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Waisman Scientists Model Human Disease in Stem Cells

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Su-Chun Zhang
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Madison, Wisconsin - Many scientists use animals to model human diseases. Mice can be obese or display symptoms of Parkinson's disease. Rats get Alzheimer's and diabetes.

 

But animal models are seldom perfect, and so scientists are looking at a relatively new type of stem cell, called the induced pluripotent stem cell (iPS cell), that can be grown into specialized cells that become useful models for human disease.

 

IPS cells are usually produced by reprogramming a skin sample into a primitive form that is able to develop into all of the specialized cells in the body. In the laboratories at the Waisman Center at the University of Wisconsin-Madison, scientists are growing iPS cells into models of disorders caused by defective nerve cells.

 

Su-Chun Zhang talks with postdoctoral student Lin Yao as she prepares stem-cell cultures in Zhang's research lab at the Waisman Center.

The technology depends on work pioneered over the past decade or so by Su-Chun Zhang, a neuroscientist who leads the iPS Core at Waisman, which also produces cells for other investigators on campus.

 

The multidisciplinary Waisman Center, now in its 40th year, combines treatment with clinical and basic research to address many of the most complex and disabling disorders of development.

 

"Animals are small and incredibly helpful," says Zhang, a professor of neuroscience and neurology, "but if we take the neurological disorders that the Waisman Center focuses on, including Parkinson's, Huntington's, retinal degeneration, ALS, spinal muscular dystrophy, Down syndrome and autism, animal models often do not precisely mimic what we see in patients."

 

Zhang was the first in the world to overcome the primary challenge for using embryonic stem cells, and now iPS cells, to model neurological disease: mastering the subtle chemical cues that force a stem cell to develop into neurons, which carry nerve signals. "Now, we can not only direct iPS cells to become neurons, but also into very defined types of neurons that are involved in the diseases that most interest us," he says.

 

In his own research, Zhang focuses on ALS (Lou Gehrig's disease) and other fatal diseases that destroy the neurons that control movement. "IPS cells can create motor neurons that grow in a Petri dish and tell you, 'I am sick.' We see the same characteristic blobs and tangles in the long fiber of the nerve cells. Something is blocking traffic so the sub-units inside the cell cannot pass through these long fibers. This is exactly what we see in patients."

 

Using iPS-derived cells, Zhang is attempting to find drugs that ease the traffic. "We can take the traffic jam and use it as a readout - a signal - in a dish, and screen as many as 1,000 compounds and approved drugs at a time, to see if we can find something that can open this traffic jam."

 

Drug screening, in fact, is only one goal of the focus on iPS cells as neurological disease models at Waisman. Read more about the scientists who are seeking new patient treatments through the use of induced pluripotent stem cells.



Date Published: 06/26/2013

News tag(s):  researchstem cells

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Last updated: 04/17/2014
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