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Research Scene

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Dr. Craig Cady, associate professor of biology, and Eliana Toren ’16 and Feras Altwal, MS ’14 use a chemical analyzer to determine critical gas concentrations necessary for growing parathyroid cells in Bradley’s Stem Cell Research Laboratory in the biology department.

A World First for Bradley: A Breakthrough in Parathyroid Disease

Biology major Eliana Toren ’16 became fascinated with endocrinology in seventh grade. A native of El Paso, Texas, Toren said, “I was and still am amazed at how hormones control every single aspect of our bodies — from our emotions, to how fast our hearts beat, to our metabolism. Every system controls every other system in our bodies in one way or another.” 

When Toren met Dr. Craig Cady, associate professor of biology, she told him of her profound interest in endocrinology. “He said he had never met a freshman who expressed this passion so keenly,” she recalled. “Then I looked at the shelves in his office and saw a sea of books with endocrinology titles.”

Spending much of her first two years at Bradley learning to conduct basic research, Toren was ready to assist Feras Altwal, MS ’14 on his graduate project in search of a solution for parathyroid disease. “About 10 percent of people with thyroid problems have parathyroid disease,” he said, adding that parathyroid cells are needed to produce hormones that generate and regulate calcium. Without fully functioning parathyroid cells, patients must take massive doses of calcium and can easily take too much or too little if not complying with a daily regimen.

Dr. Mark Holterman, professor of surgery and pediatrics at the University of Illinois College of Medicine at Peoria (UICOMP) and a close collaborator of Cady’s, encouraged Altwal to seek a cure: “Dr. Holterman explained that many of his patients suffered from parathyroid disease, which may cause muscle pain and spasms, weakened bones and more — and in children, may prove lethal.”

A mere two years later, Altwal and Toren, under Cady’s mentorship, achieved a scientific breakthrough that no one else in the world had accomplished.

The Process 

In Phase I, Altwal and Toren created parathyroid cells from adult stem cells by culturing and growing normal parathyroid cells taken from human and pig tissue. This process required experimenting with different conditions and growth factors. The pair employed three different methods in the lab; of those, only one was successful in growing normal parathyroid cells. In fact, few labs in the world have achieved this. With an awareness of the appearance of normal parathyroid cells and associated characteristics, they now have a “positive control” with which to compare the adipose (fat) stem cells they were hoping to change into functioning parathyroid cells. 

Cady noted that parathyroid cells had been created with embryonic stem cells in other labs but not with adult stem cells. One of the benefits of using adult stem cells to treat a disease is that one’s own cells are less likely to be rejected when re-implanted into the body, according to Cady. 

In Phase II, Altwal and Toren grew cultured adipose (fat) stem cells under special conditions (without antibiotics), applying special factors for several weeks to induce the stem cells to become parathyroid cells.

“Culturing and changing stem cells into parathyroid cells is a 26-day process, and we were unable to use antibiotics, which is a different and more complex protocol than most,” Toren explained. During the process, the stem cells had to be tended every day for one to five hours. “This was quite a time commitment, especially as we had several failures before we succeeded,” she remarked.

Toren said that for the first 13 days of culturing the stem cells, she and Altwal needed to stress the stem cells before differentiation. On Day 14, they added a growth medium composed of two factors that would differentiate these stem calls into parathyroid cells, and the cells began to proliferate and form colonies.

The Discovery 

Altwal remembers well the day in June 2014 when the eureka moment occurred. “I was looking through the microscope in the laboratory and saw the cells glowing green,” he recalled with unabated excitement. “This demonstrated that we had succeeded in creating the parathyroid cells.” Altwal was able to determine the successful expression of parathyroid proteins through the ELISA method, a test that uses antibodies and color change to identify a substance.

Altwal called Cady and Toren to share the astounding news: “Everyone was happy and could not have been more pleased with the outcome.”

Toren was honored to present their findings at the World Stem Cell Summit in San Antonio, Texas, in December. “I believe I was the only undergraduate presenter at the event,” she said.

Altwal, who graduated with a master’s in biology from Bradley last summer, has been working with Holterman on an immunological solution to diabetes. He will attend Rosalind Franklin University of Medicine and Science in Chicago to pursue a Ph.D. in biology in the fall.

Next Steps

Toren is continuing the research using the ELISA method to determine how fast the cells are secreting the parathyroid hormone. 

For the next step, in collaboration with a group of Bradley’s mechanical engineering students guided by Dr. Kalyani Nair, associate professor of mechanical engineering, a nanomaterial microfiber mat is being developed that could be used to return parathyroid cells to patients. 

Cady extolled the diligence and efforts of both students by emphasizing the strengths of their complementary skill sets — Altwal in clinical research and Toren in basic research: “The diverse methods they have learned in scientific research will support them in advanced research.”

The research study has been submitted to the Journal of Pediatric Surgery for publication.

The joint research grant was awarded to Bradley University and the University of Illinois College of Medicine by OSF Saint Francis Medical Center/UICOMP. 

— By Susan Andrews
— Photography by Duane Zehr