research
The Potential of a Cell

Researchers Seek a Cure for Type 1 Diabetes

Explore our search for a potential Type 1 Diabetes cure.When Jannette Dufour, Ph.D., was 13 years old, she and her family moved to Homer, a small fishing town in southern Alaska, with a population of less than 4,000. With no cable television at home, the Washington native had to create her own fun, often venturing outdoors to walk along the beach, snowmobile, fish or go cross-country skiing.

 

And when she wasn’t outside, she read.

 

“You kind of learn how to be more independent and entertain yourself, rather than just turning on the TV,” said Dufour, associate dean for research in the School of Medicine with joint appointments as associate professor in the medical school and Graduate School of Biomedical Sciences Department of Cell Biology and Biochemistry. “It was a good experience.”

 

Already interested in science at that age, Dufour believes those years of Alaskan adventure taught her critical thinking, determination and a willingness to try new things — skills she has found useful in the last 20 years researching Sertoli cells as a possible cure for Type 1 diabetes.

 

Sertoli cells originate from the male testes and protect the developing germ cells. Their ability to change immune responses and protect other cells makes them very special in the world of diabetes and transplantation research.

 

“Sertoli cells are really unique and there aren’t a lot of people that study them,” said Dufour. “So I find that fascinating, because we get to do something unique and exciting all the time.”

 

Dufour’s work is well-known in the field of diabetes research, earning recognition in publications and funding. She recently received her second National Institutes of Health grant — this one worth $448,871. Since being hired at TTUHSC in 2005, Dufour has received more than $2 million in total funding for her exploration of the Sertoli cell, which includes substantial support from The CH Foundation.

 

Dufour admits the research is hard work, and while there is still more to discover about the cell’s potential, she is determined to find the answers. Perhaps it’s just that Alaskan spirit.

 

The Problem with Islet Transplantation
The objective in Dufour’s lab is to improve the outcomes of islet transplantation. The transplantation has been shown to reverse diabetes, but with setbacks that can be harmful to the patient.

 

Islets are the insulin-producing cells in the pancreas that are destroyed in Type 1 diabetes. Individuals with brittle diabetes fulfill the criteria to receive a transplant of these cells from a donor, so their bodies might start producing insulin again.

 

Since the 1970s, scientists have been perfecting the transplantation process, but a few hurdles still remain. For example, islets are hard to come by. It takes donations from multiple human organ donors to acquire enough cells for just one transplant procedure.

 

When and if a transplant is completed, patients face another problem. The transplanted cells are from organ donors and the recipient’s immune system tries to attack them. To solve the problem, doctors prescribe immunosuppressant drugs, which Dufour said can actually be harmful in the long run.

 

“The drugs suppress the immune system,” Dufour said, “if the immune system doesn’t function properly this could potentially lead to infections and cancer.”

 

Even with a successful transplant and immunosuppressant drugs, the islet transplantation is not yet a permanent fix, with the recipient’s body eventually rejecting the cells after one to five years; resulting in the need for insulin therapy once again.

 

However, the unique makeup of the Sertoli cell offers hope for the future.

 

The Miracles and Mysteries of the Sertoli Cell

When Dufour started her postdoctoral work in 1999 at an islet transplantation lab at the University of Alberta in Edmonton, Alberta, Canada, she learned about using Sertoli cells as means to protect islets.

 

In 2005 Dufour joined TTUHSC, where she continued to research what the cell could achieve in islet transplantation.

 

Because of their protective properties against the immune system, the Sertoli cells could eliminate the need for dangerous immunosuppressant drugs after transplantation.

 

“The Sertoli cells protect themselves, yet they also protect the islets, which are the cells that are making insulin,” Dufour said. “So they have a lot of potential.”

 

Currently, Dufour’s lab performs two types of experiments: normal islet transplantation using Sertoli cells as a vehicle to protect these islets, and the transplantation of insulin expressing Sertoli cells.

 

In the Sertoli cell-islet co-transplantation experiment, Dufour said about 60 percent of the grafts survive long term, while 40 percent reject.

 

“Which is pretty amazing, because normally 100 percent of islet grafts will reject in about 20 days,” Dufour said. “And we have grafts that can survive more than 100 days.”

 

 

Gurvinder Kaur joined the lab in 2007 as a Ph.D. candidate. Now a postdoctoral research associate in Dufour’s lab, Kaur studies the Sertoli cell’s mechanism of survival and how it modifies the immune system. 

 

“If you look at the Sertoli cell survival, it’s always better than the insulin-producing cells,” Kaur said. “So if we can figure out what Sertoli cells are doing for their survival, maybe we can use those factors to improve the transplantation of other cells. For example, insulin-producing cells.”

 

So far, Dufour said they have learned Sertoli cells induce regulatory immune cells.

 

“We found that they can actually make two different types of regulatory cells,” Dufour said, “not just one.”

 

These regulatory cells are important as they are the same cells that can protect transplanted tissue and prevent autoimmune diseases, like Type 1 diabetes.

 

Meanwhile, Lea Ann Thompson, a Ph.D. candidate in Dufour’s lab and a Type 1 diabetic herself, is working on a separate, but related, project for improving treatment of diabetes: genetically engineering the Sertoli cells to produce insulin and, therefore, bypassing the islet cells altogether.

 

“(The Sertoli cells) protect themselves better than anything, so that made us think, what if we just made them make insulin?” Thompson said. “It’s very cool.”

 

So far, the Dufour lab has shown that Sertoli cells can express insulin and decrease blood glucose levels This is a very exciting step in the use of Sertoli cells.

 

With the increasing knowledge of a Sertoli cell’s survival mechanism, and the ability to genetically engineer it to produce insulin at a therapeutic level, the lab could potentially create a breakthrough in Type 1 diabetes.

 

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