Diabetes treatment

In a recently published study, researchers from the UCSD School of Medicine and scientists from the San Diego-based biotech company Viacyte, Inc. investigated methods to create endocrine cells, specifically pancreatic T-cells, which are important in treating diabetes through their production of insulin. The study compared two methods of generating endocrine cells from stem cells, in vitro (in cultures), and through transplantation of immature endocrine cells grown from mice. The malleable nature of the stem cell makes it possible to pursue both of these methods.

“The stem cell has the capacity to become any cell in the body. They will make certain decisions to become tissue or organ cells,” said Maike Sander, the principal scientist and a professor of pediatrics and cellular and molecular medicine, and director of UC San Diego’s Pediatric Diabetes Research Center.

In the research laboratory, Sander and other cellular biologists learned how to make various viable organs or tissues by recreating the same environment that the body provides. According to Sander, cells differentiate through a very specific sequence of events in the body, and scientists are taking steps to recreate these events as accurately as possible in a laboratory setting. In the lab, researchers can figure out what to do to the stem cell to make it develop like it would in the body.

In order to grow these cells, the UCSD researchers and Viacyte, Inc. scientists created their own medium to grow the stem cells and followed strict rules regarding the development process.

“One of the issues with human embryonic stem cells is that they turn into any cell in the body so there needs to be rules and protocols to make sure the cells do not differentiate until it is required,” said Allan Robins, who leads the development of techniques for cell manufacturing at Viacyte’s Georgia location.

Currently, in vitro cultivation of endocrine cells from stem cells has been an interesting obstacle to overcome.

“We don’t quite know how to execute this,” Sander said.

According to Sander, the main challenge to cultivating in vitro endocrine cells comes from correct duplication of the biological environment that triggers their differentiation. The cells they have produced in the past did not develop the primary genes essential to healthy endocrine function, such as insulin production.

However, the method of transplanting immature endocrine cells has shown promising results.

“We can [create endocrine cells] by taking a precursor, a stem cell, and putting it in the mice to grow. It takes 150 days to a year until they are matured and fully functional. [The endocrine cells cultivated from the mice] are pretty much like normal human [pancreatic] cells,” Sander said.

According to Sander, no one has attempted to transplant the immature endocrine cells from mice into humans. However, she does have an idea for how it could be done. This transplantation method is only one of many that are being tried.

“[The] best method right now is to put them into an encapsulation device, a thin membrane where the cells cannot get out but the insulin can. The cells are contained in a little membrane and the insulin [can move through it]. If anything goes wrong, you could just remove the device from the person,” Sander said.

The technique keeps in mind the experimental nature of the endocrine cells. Viacyte, Inc. aims to start human clinical trials with this method by 2014.

“We have developed our own device,” Robins said. “It’s transplanted subcutaneously. After a short amount of time the device is able to maintain the cells in the device, which then become pancreatic hormone-producing cells.”

In other developments with stem cell research and diabetes, Fernando Fierro, an assistant adjunct professor of cell biology and human anatomy at the UC Davis Institute for Regenerative Cures in Sacramento, intends to run clinical trials for mesenchymal stem cells to treat two major complications of diabetes: chronic wounds and critical limb ischemia.

“Mesenchymal stem cells are easy to grow in a culture plate. We typically obtain them from bone marrow from healthy donors, which contain a few thousands of them. After a few weeks in the laboratory, we have expanded them to several millions,” Fierro said.

At the very least, stem cell treatments for the complications of diabetes are currently in development as well.

While Viacyte, Inc. and Fierro move ambitiously to human clinical trials, Sander notes that it is important to realize that there is still much research to be done on the use of stem cells in general, and that it is important to thoroughly test every part of the process.

VICTORIA TRANG can be reached at science@theaggie.org.