Stem Cell Solutions

by Stevie Sigan

Dr. Craig Cady, associate professor of biology at Bradley University, is committed to seeking collaborative ways to treat Parkinson’s disease, heart disease and ovarian cancer—one manipulated stem cell at a time.

Dr. Craig Cady admits upfront he is not a cancer researcher. Yet in his laboratory at Bradley University, he is expanding five different lines of ovarian cancer cells. “Some of my colleagues are cancer researchers, and the more I started interacting with them, the more it turned out that cancer is very similar to injury,” he explains. “I know that stem cells can go to the injury site and replace injury—that’s how we regenerate tissue. So I thought, let’s try to see if stem cells can migrate towards cancer.”

Though Dr. Cady’s current expertise is stem cell research—a wide-reaching discipline—this is not the first time he’s ventured out of his comfort zone. Starting out as an undergraduate in zoology at the University of Wisconsin at Oshkosh, he completed his master’s degree in biology, then served as director of endocrinology at the research lab at the Medical College of Wisconsin in Milwaukee for five years. He then headed to the University of Arizona on a malaria grant, followed by a post-doctoral fellowship in Alzheimer’s and epilepsy at the SIU School of Medicine in Springfield. For that job, he “had to become a neurophysiologist, even though I wasn’t,” he admits. After accepting his current position at Bradley, he had the opportunity to get into stem cell research after collaborating with researchers in the neurology department at SIU.

With this wide-angle lens of a background, he’s developing methods to alter stem cells to function like neurons—a feat that enables them to replace damaged cells in patients with neurodegenerative diseases like Parkinson’s disease, and offers potential for use in other disorders, such as heart disease, and now, ovarian cancer.

What’s Inside That Counts
The great potential offered by stem cell research is in yielding studies to determine the complex events that occur during human development. Cancers, heart disease and Parkinson’s disease, for example, are diseases of abnormal cell division, differentiation and degenerative processes. Identifying how undifferentiated stem cells become differentiated (forming tissues and organs), as well as how cells become cancerous, or degenerate, are crucial aspects toward finding cures.

Stem cell research is also leading to the generation of cells and tissues for use in cell-based therapy—that is Cady’s main prerogative. By manipulating stem cells to act as specific cell types, it is possible to use them as a renewable source to replace the defective cells in patients with Parkinson’s, spinal cord injury, heart disease, cancer and more.

Manipulating stem cells to act as neurons is not a new mission, he explains, but the difficulty lies in proving that manipulated cells not only look like neurons, but also act like them. 

“A stem cell might look like a neuron in appearance. It might also express chemicals that are only found in neurons, but that still doesn’t tell you it’s a functional neuron,” he explains. To determine this, Cady uses a method called electrophysiology, essentially comparing the electronic fingerprints of cells. If the electronic fingerprint of a manipulated stem cell matches that of a neuron’s fingerprint, then the cell has successfully been transformed into a neuron—it not only looks the part, but will also function as a neuron.

The process to come by such data is tedious and requires the use of very expensive equipment. But the end result is solid proof or denial of true neuron functioning—evidence leading one step closer to animal trials, then human trials and feasible cures.

iPS Cells and Small Strides
Dr. Cady uses a variety of stem cells in his lab—human core blood, bone marrow, stem cells from fat, and the highly coveted iPS, or induced pluripotent stem cells. Derived from normal adult stem cells, iPS cells are genetically manipulated to express the same genes, proteins, expression and functioning as embryonic stem cells, but without the controversy.

“They are as powerful as embryonic stem cells and you can harvest them from individual patients. It’s now easy enough to do that,” Cady explains. “You can take a skin cell from a patient with heart disease, make iPS stem cells…change them into heart cells, inject them into the patient, and there’s no tissue rejection. There’s a fabulous potential use.”

The creation of iPS cells is a new feat. First produced in 2006 from a line of mouse cells by a scientist at Kyoto University in Japan, Dr. Robert Thompson at the University of Wisconsin followed suit, creating the first iPS cells from human cells in 2007. It is no coincidence this work took place at Cady’s alma mater. He trained for a week in Dr. Thomson’s laboratory, learning the “incredible technique.”

“He was the father of embryonic stem cells, and it was quite the experience,” he recalls. In the summer of 2011, he had an opportunity to purchase a line of iPS cells from Dr. Thompson’s lab. After some initial trial and error, Dr. Cady and his students have now successfully expanded the line of iPS cells in his Olin Hall laboratory, and he is very close to generating beating heart cells from the iPS cells in culture. He hangs a photo of the successfully expanded cells on his office door—a rare milestone in a line of work that demands patience and offers few daily rewards.

“It’s been very gratifying to see this kind of progress in an area that’s very difficult—cancer and heart failure in humans are really tough diseases. You have to be patient or you couldn’t do this work,” he explains.

Stem Cells for Cancer Treatment
Despite no prior cancer research history, Cady’s start with ovarian cancer research was no accident: he sought it out. One of his colleagues is in gynecology, and they got to talking. Curious if his stem cells could be manipulated to target cancer cells, he asked her which cancer is the worst.

“The cure or outcome for advanced ovarian cancer hasn’t changed in 30 years,” says Cady. “It’s really a shock to me that we haven’t made an improvement, so, I said, ‘Okay, let’s try ovarian cancer.’”

He received five lines of ovarian cancer cells, and spent two years showing that he could get stem cells to migrate toward them. Dr. Cady and his team hope to inject a “cocktail” of genetically engineered stem cells containing special enzymes into the ovarian cancer host. The stem cells will penetrate the tumor at its site. Then, an administered pro-drug will initiate a reaction with the enzyme release, converting the pro-drug into a highly active chemotherapy drug. This is a cell-based therapy.

“Ovarian cancer is a hidden disease,” he explains. “If it’s detected early, the cure rate is pretty good. But if it’s not—and most are not—it’s very difficult to deal with because it metastasizes.

“So, this is a very exciting model to me. …We gave a presentation in Chicago to some gynecologists and obstetricians, and their only current tool for advanced ovarian cancer is chemotherapy. They were quite excited about the concept we presented.”

Stem Cells for Heart Disease
Dr. Cady is also excited about the potential of his research for heart disease. Working with a cardiothoracic surgeon at Emory University, he developed a concept to surgically inject a massive amount of stem cells into the heart’s ventricle, directing them towards the heart’s tissue and blood vessels. The goal is to re-vascularize the stressed areas—to get blood back to them and regenerate new heart cells. To counter stem cells’ natural tendency to “spread all over,” they are also injecting them with nanofiber material, so they stick to their intended target.

“We induced heart failure in sheep, and their heart function dropped down to 50 percent,” Dr. Cady explains. “After the injection, we followed the sheep with echocardiogram—and heart function went back up to 90 percent following our injections—a 40 percent improvement.”

This is a phenomenal finding in heart failure research, where the only current option for treatment is to slow the load on the heart, which only decreases the rate of inevitable deterioration. The only real cure is a heart transplant, which is not performed routinely.

Dr. Cady points to the photo on his door. “They start out like this—growing up in clusters or colonies, then you…separate them, and put them into a well with 1,500 inverted pyramids. All of the cells fall into place and form little clusters. Those are the cells that change into heart cells, if you get the right ingredients. Some of the ones on the peripheral are starting to beat a little,” he smiles. “We aren’t there yet, but we hope we are soon.”

Collaboration is Key
In addition to his work with collaborators at SIU and Emory, Dr. Cady is now working closely with colleagues in Bradley’s engineering department to get a better grasp on other potential uses for nanomaterials.

“The environment at Bradley is very open and it’s encouraged to work with other departments,” he says. He is also awaiting word on a grant proposal he submitted with an orthopedic surgeon at SIU to create a 3-D nanomaterial model to replace skin, muscle and nerve tissues in major trauma patients. “It’s the first time it’s been done, so I’m keeping my fingers crossed,” Cady says.

Without grants and funding, his hands are tied. “Those of us in science, we need the expensive instruments to do what we do. If we have those on campus, that’s going to make a really big difference,” he explains. And not just for the scientists.

“A lot of people don’t realize that the basic sciences and grants in science support the community in a big way,” he explains. “Federal grants…bring a tremendous amount of money to the local community”—not only to support research and the purchase of exotic technical equipment, but also “to students, laboratory technicians, local computer support…The local community is strongly affected by [the grants], in addition to the notoriety…that we’re doing research like this here in Peoria.” iBi

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