Using genetic modification to protect beta cell transplants

One of the most promising treatments for type 1 diabetes in recent years has been islet transplantation – the transfer of insulin-producing cells from a donor’s pancreas to a person with type 1 diabetes (T1D), eliminating the need for insulin injections. This therapy can provide more flexibility with meal planning due to the active regulation of blood sugar levels, and also help protect against serious long-term complications, including heart disease, kidney disease, and nerve and eye damage.

However, some limitations remain such as the supply of donor transplants, the need for lifelong immune suppression and graft failure. These occur when the cells are not protected from immune attack and are unable to form the necessary blood vessel networks they need to thrive and provide insulin to patients.

Dr. Shugo Sasaki, a JDRF-funded investigator and a postdoctoral fellow at the University of British Columbia, is currently testing human embryonic stem (hESC)-derived surrogate beta cells that produce a specific protein (CCL22), which helps protect beta cell transplants from death and dysfunction. Along with his team, he hopes to determine whether or not the genetic modification of insulin-producing cells leads to better success with transplants for people with T1D who receive beta cell replacement therapy.

 

“Specifically, we are editing the stem cells to produce CCL22 that can protect cells from immune attack,” explains Dr. Sasaki. “If successful, we can then edit other parts of stem cell-derived insulin-producing cells to get optimized beta cells.” 

According to Dr. Sasaki, recent findings reveal that the engineering of insulin-producing cells may preserve the function and survival of hESC-derived beta cells following transplantation, thereby removing the risk of life-threatening health issues and hypoglycemia (low blood sugar).

To date, more than 800 islet transplants have been performed all over the world. Given the rising incidence of T1D, Dr. Sasaki believes that new protocols must be developed in order to generate insulin-producing cells from human pluripotent (self-replicating) stem cells.

“As a practicing endocrinologist in Japan for 10 years, I felt patients could benefit from a safer and more efficient therapy beyond insulin injection because many had difficulty with blood glucose control and experienced complications,” he relates. “Cell therapy for diabetes is very promising, which is why I came to Canada to learn more about stem cell-engineering. Medicine is an art based on science, and science makes miracles.”

If this approach is effective, the results of Dr. Sasaki’s study will further the optimization of functional and immune-tolerant surrogate beta cells, which will help pave the way towards a cure for T1D.

Lets turn type one into type none