Diabetes: help yourself
Biology textbooks teach us that adult cells throughout life retain the identity acquired as a result of differentiation. However, Swiss researchers from the University of Geneva, working under the leadership of Professor Pedro Herrera, have recently demonstrated that the adaptive capacity of cells is much higher than we think. They managed to teach initially non-insulin-producing pancreatic cells to ensure stable production of this hormone. Moreover, it is quite possible that such plasticity is not an exclusive property of pancreatic cells.
The human pancreas contains several different types of endocrine cells (alpha, beta, delta, epsilon and gamma cells) that produce various hormones responsible for regulating blood glucose levels. These cells are grouped into small clusters known as pancreatic islets or Langerhans islets. Diabetes mellitus develops in cases when, in the absence of functional beta cells, the regulation of blood glucose levels is disrupted.
In earlier experiments on mice, the authors demonstrated that the pancreas has the ability to produce new insulin-producing cells by spontaneously changing the identity of other cell types. As part of the next study, they decided to find out whether human cells have this ability and whether it is possible to cause such a transformation artificially.
The Langerhans islands of patients with diabetes mellitus and healthy people were chosen as the object of the study. First, the authors sorted the cells by type in order to be able to work with two types: alpha cells (producing glucagon) and gamma cells (producing pancreatic polypeptide). The resulting cells were divided into 2 groups; one group was marked only with a fluorescent marker, and in addition to the marker, genes encoding insulin transcription factors specific to beta cells were inserted into the other.
After that, they constructed "pseudo-islands" consisting of one type of cells, which allowed us to accurately study the behavior of cells of each type. According to the observations made, the very fact of cell aggregation, even into monotypic pseudo-islands, stimulates the expression of certain genes associated with insulin production, as if "non-beta" cells naturally feel the absence of beta cells and take over their function. However, to launch insulin production, researchers had to artificially stimulate the expression of one or two key beta cell genes. A week after the start of the experiment, 30% of the modified alpha cells had already produced and secreted insulin in response to glucose exposure. Gamma cells transformed under the same conditions and secreted insulin even more actively.
Pseudo-islets of human alpha cells of the pancreas. These cells produce glucagon (blue), but can "learn" to produce insulin (red). Green fluorescent protein (green color) allows you to track the origin of cells to confirm the change of their identity.
At the second stage of the work, the authors transplanted the obtained monotypic pseudo-islets from modified human cells to mice with simulated diabetes mellitus. This cured the animals of the disease, and with the subsequent removal of cell transplants, they, as expected, began to show symptoms of diabetes again. Moreover, the pseudo-islets from the modified cells retained their ability to produce insulin in response to an increase in glucose levels for at least six months.
The authors also note that when working with cells from both healthy and diabetic donors, comparable results were obtained, which demonstrates the preservation of cell plasticity in disease.
A detailed analysis of the trasformed alpha cells showed that they retain an identity close to that of the original cells. In autoimmune diabetes (type 1), beta cells are destroyed by the patient's own immune system. The researchers suggested that the transformed cells would be resistant to the effects of immunity due to their difference from beta cells. To test this hypothesis, they conducted their joint cultivation with T-cells of patients with type 1 diabetes mellitus. Subsequent observations have shown that such cells cause a very weak immune response and may possibly be more resistant than the original beta cells.
To date, pancreatic transplantation is carried out only in particularly severe cases of diabetes mellitus, while the preferred approach, due to less invasiveness, is the transplantation of islets, rather than the whole organ. This technology is very effective, but it has its limitations: like any transplant, it requires immunosuppressive therapy. In addition, the transplanted cells are destroyed within a few years.
According to the authors, in this situation it makes sense to use the body's own regenerative abilities. However, there are still many difficulties to overcome before the implementation of their proposed approach into clinical practice. To begin with, it is necessary to find a way to pharmacologically or genotherapeutically trigger the mechanism of changing the identity of the cells of the patient's own pancreas without undesirable effects on other cells of the organ.
Article by Kenichiro Furuyama et al. Diabetes relief in mice by glucosesensing insulin-secreting human a-cells is published in the journal Nature.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Geneva: Diabetes: human cells can also change jobs.