The researchers modified T cells, a type of lymphocyte (pictured above), to protect pancreatic cells. (Image credit: Jian Fan via Getty Images)
Scientists have created immune cells for the first time that can protect stem cell transplants from being rejected by the body, in a move that could lead to a future treatment for diabetes.
The new cells, which can protect insulin-producing cells transplanted into mice, serve as an early “proof of concept,” said study co-author Audrey Parent, an assistant professor in the University of California, San Francisco (UCSF) Diabetes Center.
If proven safe and effective in humans, these customized cells could one day be used to protect transplanted tissues from immune attack, reducing or eliminating the need for immune-suppressing drugs. This, in turn, could pave the way for a cure for diseases such as type 1 diabetes.
In type 1 diabetes, immune cells known as killer T cells destroy the insulin-producing beta cells in the pancreas. In recent years, scientists have been getting closer to replacing the destroyed beta cells with new cells derived from stem cells, which can turn into any type of cell in the body.
In June, for example, scientists reversed type 1 diabetes in a man by reprogramming his fat cells, and Boston-based Vertex Pharmaceuticals recently launched a large-scale study to test whether reprogrammed stem cells can eliminate the need for insulin in people with type 1 diabetes.
But before such stem cell transplants can become widely available, scientists need to solve a major problem: In type 1 diabetes, killer T cells are trained to target beta cells and have already destroyed these cells. The transplanted cells need protection from this immune attack, so patients currently require powerful immune-suppressing drugs. However, these drugs leave patients vulnerable to dangerous infections and can be toxic to the kidneys and other organs.
To overcome this problem, Parent and her colleagues created T cells in the lab that protected the transplanted cells—known as the graft—from attack.
“We took an immune cell and changed its machinery so that it became a defense cell rather than a killer cell,” Parent told Live Science. “And then we directed it to the transplant.” In essence, the customized cells act as bodyguards.
The bodyguards target beta cells because they recognize a specific protein called CD19 that the researchers added to beta cells. When the bodyguard cells grab CD19, they begin producing a molecule that inhibits killer T cells.
The guards also produce a protein that soaks up an inflammatory chemical that normally triggers the activation of killer T cells. This anti-inflammatory protein also stimulates the guards to multiply, creating a positive feedback loop that strengthens their ranks, Parent noted.
To test their guardians in a living organism, the researchers took beta cells derived from stem cells and implanted them in mice. They then allowed the killer T cells to attack the transplanted beta cells. One group of mice was also injected with their customized cells to guard the transplants.
In mice that were not given the customized cells, the killer cells quickly wiped out all the beta cells. But in mice that were given the customized cells, the transplants lasted for at least 35 days, during which time the mice continued to produce insulin, according to a study published Thursday (Dec. 5) in the journal Science.
Parent said the results show that it is possible to create T cells that can protect transplanted tissue.
However, one of the challenges, Parent said, is identifying a unique protein target to activate the customized
Sourse: www.livescience.com
