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The Future of Regenerative Medicine Is Now

While many researchers spend their entire careers hoping to achieve just one life-altering breakthrough, Dr. Craig Cady, associate professor of biology at Bradley, contributed to two medical advances in one year.

Cady, who is well known for his work with stem cells, specializes in regenerative medicine. Whether he is differentiating induced pluripotent stem (iPS) cells or assisting with a medical procedure, Cady’s research already is helping humankind.

Differentiating Cells to Cure Disease

Understanding iPS Cells

Like embryonic stem cells, iPS cells are capable of becoming any cell in the body, allowing scientists to avoid the ethical issues traditionally associated with embryonic stem cell research because iPS cells are made from adult cells. And, because an adult’s own cells could be used to generate iPS cells, an individual could have new cells made without the risk of tissue rejection. View a video of Dr. Craig Cady discussing his stem cell research and see the beating heart cells created in his lab at bradley.edu/go/works-Cady2014.

Since bringing iPS cells to the University three years ago, Cady and his student research assistants have embarked on the challenging task of differentiating, or transforming, the generic cells into specific functioning cells. Last spring, one of the studies performed by his students Kate Lipovsky  (pictured above with Cady) and Erin Koch resulted in his lab’s first real success in this area — the creation of beating heart cells.

After beginning with a 3-D form that cultures iPS cells in an orb-like cluster called an embryoid body (due to its similar appearance to an embryo), Lipovsky and Koch only achieved limited beating on the periphery. They then changed their approach to a monolayer, or “sandwich,” form that is grown flat in a dish.

Because their monolayer protocol was based on one published at the University of Wisconsin, Madison, they expected to see maximum beating at Day 9. For 17 days, they considered starting over … until Lipovsky discovered beating on Day 26. “It’s really moving to see; it’s almost emotional,” Cady said of the achievement. “Frankly, in the laboratory, to see striking results is quite rare. We’re usually looking at data points on a graph; this is on a different level.”

Although the cells’ synchronized beating was evidence that the team had created both human heart and pacemaker cells, a verification process confirmed that fact. The routine procedure called immunocytochemistry binds antibodies with specific fluorescent color tags to the cells’ proteins. If successful, the cells will appear with those specific colors when evaluated under a fluorescent light microscope, which is exactly what happened in Cady’s lab.

Fighting Parkinson’s

Dr. Craig Cady heavily focuses on Parkinson’s disease research in addition to heart disease. In fact, his student research assistants plan to try differentiating iPS cells into dopaminergic neurons. Since patients with Parkinson’s have a lack of dopamine in their brains, the creation of dopamine-producing neurons would be the first step toward finding a treatment — or possibly a cure — for the devastating movement disorder.

The hope for this research is that it could one day lead to a treatment for heart failure — the leading cause of death in the United States. According to Cady, “All cardiologists can do now is keep giving patients drugs to reduce the stress on their hearts. Eventually, they die unless they receive a transplant.” That is until the iPS differentiating procedure is perfected.

Imagine someone has a heart attack. The physician could collect some of the person’s skin cells and insert the four stem cell-associated genes into them to produce iPS cells. Then, the iPS cells would be differentiated into new heart cells — customized to the individual’s body — that could be injected into the heart to repair the damage, all without the risk of rejection.

Applying Skill to Give New Hope

Two-year-old Hannah Warren was the world’s youngest recipient of a bioartificial trachea. The transplant surgery — conducted at the Children’s Hospital of Illinois in Peoria — was performed by a world-class team of doctors with an assist from Dr. Craig Cady, associate professor of biology at Bradley, and his graduate research assistant, Feras Altwal. The men helped evaluate the health and expansion of the cells implanted on the nanofiber trachea before the procedure. Photo courtesy OSF/Jim Carlson.

Due to his experience working with stem cells, Cady was recruited for a pivotal role in a groundbreaking surgery that occurred in April 2013. He provided the technical expertise necessary to successfully generate a tissue-engineered bioartificial trachea for transplant into 2-year-old Hannah Warren — the first such transplant in the United States.

When Warren was born, the doctors in her Seoul, South Korea-based hospital noticed she was blue and immediately inserted a tube from her throat to her lungs, so she could breathe. A CT scan revealed she was born with tracheal agenesis — the lack of a complete trachea. This condition required Warren to have both breathing and feeding tubes to live.

Dr. Mark Holterman, a pediatric surgeon at Children’s Hospital of Illinois, learned of Warren’s plight while on a business trip in Seoul. He soon returned to meet with her parents, Darryl and Young Mi, offering to help find a solution that might save the girl; it took him two years to make the surgery a reality.

As the only tracheal implant surgeon in the world, Dr. Paolo Macchiarini, professor of regenerative surgery at the Karolinska Institute in Stockholm, was vital to the procedure. He quickly agreed to lead the surgery and donate all his time with additional assistance by Dr. Rick Pearl, head of pediatric surgery at the Children’s Hospital. Keith Steffen and Margaret Gustafson, CEO and president at OSF Saint Francis Medical Center and the Children’s Hospital respectively, then gave approval to move forward with the surgery in Peoria, with OSF agreeing to assume all costs. The next challenge was finding the right nanofiber material for the trachea and obtaining FDA approval, which was granted due to Warren’s otherwise low hope of survival.

Cady and his lab were the final pieces of the puzzle. Applying his expertise in stem cell biology, he helped complete the trachea’s preparation. Warren was given G-CSF, a drug to induce stem cell production in the blood. The team waited five days before collecting and isolating the cells used to line the nanofiber trachea, a process that was performed inside an ultra-sterile bioreactor created specifically for this purpose by the BioSpherix company of Lacona, N.Y.

On the morning of the surgery, Feras Altwal, Cady’s graduate research assistant, collected some cells from the bioartificial trachea and delivered them to Cady in his Olin Hall lab for evaluation. Using a live/dead assay, Cady determined the cells had attached and were healthy and expanding, so he made the final call to say the surgery was a go.

Nine hours later, the procedure concluded, and the entire team waited. In the following weeks, Warren’s recovery was slow and steady. Eventually, her parents could sleep in the same room with her and her grandparents could touch her, all for the first time. She also tasted her first lollipop, actually walked down the hall, and experienced something she never imagined —petting a dog.

Unfortunately, Warren died on July 6 due to complications found during, but not related to, her surgery. Her passing devastated not only those directly involved in the transplant but everyone who followed her story in the international news. However, her parents, the doctors, and researchers believe it was worth it, with Cady later commenting on her immeasurable contribution to the field of regenerative medicine: “She and her family were pioneers. Hannah was a great inspiration to the team.” In the end, her surgery showed the world that using a patient’s own stem cells is now a real and viable medical option.

Having learned so much in the process, Cady is part of a group working to establish a regenerative medicine team in Peoria, which he believes is the next logical step in advancing this field. “Due to the need for multiple areas of advanced expertise and the high cost of the latest medical technologies,” he explained, “the formation of collaborative, high-performing teams is essential.”

Tackling New Challenges

Despite all his success to date, Cady continues to seek answers to the complex questions in medicine. He will use every technology available to him to realize more advances right here at Bradley: “Large institutions certainly contribute to the field of neuroscience or heart research or cancer, but the smaller institutions also have a voice and can contribute to this area … and I think we’ve made some great progress.”  

By Clara Miles
Photography by Duane Zehr