A team from the National Cancer Research Center (CNIO) led by Manuel Serrano has been the first in the world toachieve that adult cells of a living organism regress in their evolutionary development until they recover characteristics of embryonic stem cells. As explained by the authors of the work in the magazineNature, research has also revealed that these embryonic stem cells obtained directly within the body have abroader differentiation capacity than those obtained by in vitro culture. Specifically, they have characteristics of cellstotipotentes, a primitive state never before obtained in a laboratory.
Embryonic stem cells are the main bet for thefuture regenerative medicine. They are the only ones capable of generating any cell type of the hundreds of cell types that make up an adult organism, which is why they constitute the first step in curing diseases such asAlzheimer’s, Parkinson’s, or diabetes. However, this type of cell has a very short existence, limited to the first days of embryonic development, and does not exist anywhere in the adult organism.
One of the major milestones in recent biomedical research was the one carried out by Shinya Yamanaka in 2006, when he managed to create embryonic stem cells (cIn vitro induced pluripotent stem cells, or in vitro iPSCs) from adult cells, using a cocktail of just four genes. Yamanaka’s finding, for which he was awarded the Nobel Prize in Medicine in 2012, opened a new horizon in regenerative medicine.
Now, CNIO researchers have gone one step further by achieving the same as Yamanaka but within the body itself, in mice, without the need to go through in vitro culture plates. Generating these cells within an organism brings this technology even closer to regenerative medicine.
The first challenge for the CNIO researchers was to reproduce Yamanaka’s experiment in a living being. For this they chose the mouse as a model organism. Usinggenetic manipulation techniques, the researchers created mice in which all four Yamanaka genes can be activated at will. When they turned on these genes, they observed that adult cells were able to regress in their evolutionary development to embryonic stem cells in multiple tissues and organs. “This change of direction in development has never been observed in nature; We have shown that we can obtain embryonic stem cells also in adult organisms and not only in the laboratory ”, explains María Abad, co-author of the work. Manuel Serrano adds: “Now we can begin to think about methods to induce regeneration locally and temporarily in a certain damaged tissue.”
The stem cells obtained in the mice also had totipotency characteristics never generated in a laboratory, equivalent to those of human embryos of 72 hours of gestation , composed of a mass of only 16 cells. In comparison with the cells obtained with the technique developed by Yamanaka, the stem cells obtained at the CNIO thus represent an even earlier embryonic stage, with greater differentiation capacities . So much so that the authors were even able to induce the formation of pseudo-embryonic structures in the thoracic and abdominal cavities of the mice.
“Our stem cells also survive outside mice, in culture, so we could also manipulate them in the laboratory,” explains Abad, who assures that “the next step is to study whether these new stem cells are capable of generating a more efficiently forms different tissues, such as pancreas, liver or kidney ”.
