20 November 2017

Re-education of lymphocytes

A group of scientists from Harvard Medical School in a study on mice has developed a way to modify the body's own stem cells, which will lead to increased synthesis of the PD-L1 protein, which suppresses excessive activity of the immune system.

In diabetes mellitus 1, due to the death of beta cells of the pancreas, the level of insulin in the blood decreases. Glucose coming from food is not absorbed by cells and is not converted into energy, but remains in the blood (hyperglycemia). Constantly elevated blood glucose levels lead to numerous complications, such as decreased vision, the formation of non-healing trophic ulcers, polyneuropathy, nephropathy, and others.

It has been proven that a defect of the immune system is crucial in the development of type 1 diabetes mellitus: T-lymphocytes, normally protecting the body, take beta cells of the pancreas for foreign agents and attack them. The causes of the defect are unknown. Perhaps some virus is to blame, which, in the presence of a hereditary predisposition, triggers this autoimmune process.

The existing treatment of diabetes mellitus consists in the constant administration of insulin and is aimed at combating the consequences, but researchers do not lose hope of completely curing the disease by eliminating its cause.

There have been attempts to do this in various ways, for example, to use cytostatic drugs that inhibit the cellular activity of T-lymphocytes, to develop vaccines aimed at changing the immune response, to inject cord blood stem cells.

The most promising method seemed to be the introduction of their own hematopoietic stem cells in order to "reboot" the immune system, but it was not effective enough.

In a new study, a group of scientists led by Paolo Fiorina found the reason for the ineffectiveness of such therapy. It was found that in diabetes mellitus, hematopoietic stem cells have a defect: they stop producing the PD-L1 protein. This protein suppresses T-lymphocytes, preventing their excessive activity, and thus supports the immune system in balance.

In mice with diabetes, the expression of genes encoding PD-L1 protein synthesis in hematopoietic stem cells differed from that in healthy mice. This difference led to a significant decrease in PD-L1 levels even in the early stages of diabetes.

The researchers subjected the stem cells to genetic modification, restoring PD-L1 protein synthesis, and tested them on mouse and human cells. In both cases, the modified blood stem cells caused a decrease in the inflammatory response by suppressing the immune response.

When ingested in mice with diabetes, the modified stem cells migrated into the pancreatic tissue, which was accompanied by a short-term decrease in blood glucose levels. The long-lasting effect (until the end of life) was preserved in a third of mice. The results of the experiment prove that modified stem cells cause a restructuring of the immune system.

The advantage of this method of diabetes treatment is the theoretical absence of side effects, since the body receives its own stem cells after modification.

The researchers experimented with two ways to activate PD-L1 synthesis: the gene therapy described above and the regulation of the protein mechanisms of cells using a "cocktail" of three small molecules. Both methods were equally effective in restoring pancreatic function.

Together with a private company, they are looking for ways to improve the second treatment method and hope to move on to its clinical trial.

The article Moufida Ben Nasr et al. PD-L1 genetic overexpression or pharmacological restoration in hematopoietic stem and progenitor cells reverses autoimmune diabetes is published in the journal Science Translational Medicine.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Medical News Today: Type 1 diabetes: Could modified blood stem cells lead to a cure?

Found a typo? Select it and press ctrl + enter Print version