Rensselaer Magazine Winter 2007-08 - "Closing the Stem Cell Gap" Page 3

Linhardt, whose lab studies complex carbohydrates in stem cells, says collaboration is key to stem cell research results. “Through some unique collaboration, our researchers are developing critical tools and technologies that are sorely needed to quickly advance stem cell research.”

While Plopper began his career in medical schools surrounded by other biologists, he now works alongside engineers and computer scientists on stem cell research. “Here I am no longer asking questions in such a way that it requires a biologist to answer them. I am interested in the biology, but at the same time, I have learned since being at Rensselaer that I can actually get answers to questions, or I can even ask questions that never occurred to me until I met people in other disciplines.”

Plopper is working to determine what controls cell behavior. This is particularly important when it comes to stem cells because if researchers understand what makes stem cells differentiate into a muscle cell rather than a heart cell, they could someday be able to develop methods to control the differentiation. And potentially target and heal damaged tissue.

When Plopper described his research on cell development to Associate Professor of Computer Science Bulent Yener, the two had an epiphany. Yener, who developed complex computer algorithms to model the structure of the Internet and to discover hidden communication patterns in cyberspace, realized that his mathematical techniques could be applied to model the differentiation process in stem cells and discover hidden relationships among the cells during this process. Today, Plopper and Yener, along with Professor of Mathematical Sciences Kristin Bennett, are fusing biology and biocomputation to predict what causes stem cells to differentiate and model how decisions are made in the cells.

“They rely on me to provide the biology,” Plopper says. “And I rely on them to provide me the answers.”

Like Yener, Deanna Thompson, assistant professor of biomedical engineering, whose main research focuses on the nervous system and spinal cord injury, did not expect to take on stem cell research when she arrived at Rensselaer. “By being here and interacting with senior faculty and other faculty, I am using the tools that I have as an engineer in a different way,” Thompson says. “By working with biologists and other engineers I was able to find my own niche in stem cell research efforts that I might never have considered without the larger support of the biotechnology community at Rensselaer.”

Thompson is now working to grow rare neural stem cells, which eventually will become mature and healthy brain cells. To harness the potential of neural stem cells, Thompson isolates the cells and grows them in culture with other cells found in the neural stem cell niche. Controlling their growth outside the body will help Thompson develop a better understanding of the microenvironment or niche that surrounds neural stem cells inside the body and likely directs their development.

Deanna Thompson and Lee Ligon

“New York state has provided strong support to Rensselaer’s biotechnology effort.

Now, the state is working to fill in the massive gaps left by the 2001 federal restrictions. This is an important step toward recruiting top stem cell researchers to the state,” says Provost Robert Palazzo.

Research from Sally Temple, a stem cell biologist at the New York Neural Stem Cell Institute, has shown that neural stem cells are typically found near blood vessels. The outer surface of blood vessels is composed of a specialized type of cell called endothelial cells. Thompson is looking at how an artifical niche composed of endothelial cells in different configurations impacts the neural stem cell growth and differentiation.

“If we can develop a reliable source of neural stem cells, we might some day be able to develop regenerative therapies using stem cells that can repair traumatic brain and spinal cord injuries,” she says.

Lee Ligon, assistant professor of biology, is using Thompson’s specialized growth substrates to further understand the stem cell niche. Little is known about why an undifferentiated stem cell will either divide to form another stem cell or begin to differentiate into another, more specialized cell. Current research supports the idea that the environment around the stem cell or the stem cell niche directs the stem cell’s development.

Ligon is manipulating the shape of growth substrates around cells to see how that affects their development. She is working to determine how a change in the shape of the stem cell niche could alter a stem cell’s fate.

A stem cell niche is believed to be similar to a hole in the dirt with stem cells resting at the bottom like small seeds, full of potential and ready to grow. The stem cells will either divide to become more undifferentiated stem cells or move toward the surface of the niche, becoming more differentiated as they get further outside the hole like a cellular sapling — no longer a seed, but not yet a tree.

“The differentiation of stem cells is believed to depend in part on their geometry, in particular their orientation in space when they divide,” Ligon says. When they divide in a plane perpendicular to the bottom of the niche, the cells split horizontally, creating more stem cells. When that plane is parallel to the bottom of the niche, they split vertically, creating more differentiated cells.

Ligon is working to test the theory about the geometry of cell division by growing cells in bio-engineered micro-environments of different sizes and shapes. “If we can understand what causes normal healthy stem cells to differentiate, we can hopefully someday uncover the potential errors that occur in the division and differentiation process and cause disease,” she says.

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