This type of diabetes occurs when the immune system attacks the insulin-producing cells in the pancreas, mistaking them for foreign invaders. With the loss of these cells, the body is unable to produce insulin and regulate blood sugar levels.
The researchers were able to protect the mice from the disease or cure them completely by combining the transplantation of two types of cells: blood stem cells (which make up the immune system) and pancreatic islet cells (which produce insulin), from immunologically incompatible donor mice - something in which it is normally expected that the body would reject these cells or that the transplanted immune cells would attack the recipient's tissues.
But surprisingly, this did not happen at all; none of the mice contracted graft-versus-host disease, in which new immune cells appear to attack the recipient's healthy body tissues.
The mice's original immune system also stopped destroying the islet cells, and after transplantation the animals did not need any immunosuppressant drug or insulin for six months, which is a long time in the life of mice.
This success is attributed to the fact that the mice developed a hybrid immune system, combining cells from the donor and cells from the recipient, which "re-trained" the immune system to stop attacking pancreatic cells.
"The potential for these findings to be applied to humans is extremely exciting," said Dr. Sung K. Kim, a leading scientist in medicine, endocrinology, and aging and director of the Stanford Diabetes Research Center.
He explained that the basic steps used in the experiment are already being applied in the treatment of other diseases, which increases the likelihood of transferring them to human use in the future.
This experiment complements the results of a study conducted in 2022, in which researchers deliberately caused mice to develop diabetes using toxins that destroy islet cells, and then transplanted stem cells and islet cells from another donor, after giving them a mild initial treatment.
But the challenge in the new study was much greater: dealing with true autoimmune diabetes, that is, a disease that occurs spontaneously due to an immune attack on the islet cells without external intervention.
In this case, the cultured islet cells face two problems:
These are foreign cells that the body may reject.
It is also prone to repeated autoimmune attacks.
To solve the problem, researcher Praksha Bhagchandani and her colleague Stefan Ramos added a drug commonly used to treat autoimmune diseases to the initial pre-transplant therapy. With this modification:
The researchers prevented the mice from developing autoimmune diabetes.
All nine mice with long-standing diabetes were cured after transplantation of stem cells and islet cells together.
These are rare results in the treatment of a highly complex disease.
The researchers emphasize that all the drugs and treatments used in this trial are already being used in human clinics for stem cell transplants, and this increases the likelihood of moving to human trials.
Despite the great success, significant obstacles remain:
Pancreatic islet cells are extracted only from deceased donors.
Islet cells and stem cells must come from the same donor in order for the body to accept them.
The amount of islet cells from one donor may not be enough to treat one diabetic patient.
Now, scientists are looking for ways to overcome these obstacles, such as:
Producing large quantities of islet cells in the laboratory using human stem cells.
Improving methods for protecting transplanted islet cells to increase their survival in the body.