in 2009 was achieved simply reprogram adult skin cells to transform into pluripotent stem cells or iPS, as versatile as embryonic stem cells, this procedure was always performed in the laboratory.
A team from National Cancer Research Centre (CNIO) has shown, for the first time that the process of turning the clock of adult cells (reprogram) to turn them into iPS can also cause the body of a living adult. But in addition, these stem cells, which have been developed in mice have a greater capacity for differentiation (to become different tissues) than that obtained in the laboratory. This new technique has no direct therapeutic impact. But lets think about the future, even distant, which are themselves damaged organs which can produce stem cells to regenerate.
“It’s an outstanding job,” muses Juan Carlos Izpisúa, director of the Center for Regenerative Medicine in Barcelona. “It opens a new era for medicine, the search for strategies that allow us to regenerate organs and tissues in a manner similar to natural processes.”
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group work Manuel Serrano, director of the Molecular Oncology Program at the CNIO, is published by Nature and part of the technique that allowed the Japanese researcher Shinya Yamanaka iPS obtain stem cells in 2007 and the Nobel in 2012.
Yamanaka reprogrammed
introducing adult cells including four genes characteristic of embryonic stage, so that, when activated, the cell returns to a state substantially equal to that of an embryonic cell, making the famous iPS. Serrano has used the same combination of genes, called Yamanaka cocktail, but has given several twists with surprising and unexpected results.
The Spanish investigator a mouse designed to introduce an artificial gene, in response to administration of an antibiotic, tetracycline-activated and produces the same effect as the cocktail of the four Yamanaka proteins.
Serrano’s original intention was not to generate iPS stem cells within rodents, but something “more prosaic” as moving this newspaper. I was looking for a simple way to obtain embryonic stem cells. And the manner of attaining cells was removed from the mice with the modified genome, bathe in a laboratory dish with the antibiotic and easily generate iPS cell cultures.
But at one point, I doubt arose. What would happen if the antibiotic was given directly to the genetically modified mouse and not your cell cultures? “Honestly, we did not trust that were to reprogram cells in the mouse,” the researcher moves. “We did not think it would work,” he insists. But it worked.
Serrano modified mice drank the antibiotic diluted in water for a week. When launching the mechanism described by Yamanaka and adapted by the CNIO, the researchers found that adult cells from mice lost their characteristics and traits acquired embryonic cells “that do not exist in adult organisms,” said Serrano.
After rewind, and become deprogrammed stem cells, cells and replicate in an uncontrolled manner inside the disordered body rodent species giving rise to a mass composed of various tissues (brain, muscle, bone, intestine. ..) tissue. A kind of disorganized embryo called teratoma.
The importance of these structures tens pseudoembrionarias who appeared in the thorax and abdomen is not in clinical use. No therapy can happen to cause teratomas. What is relevant is that in this way it was evident the high differentiation ability of stem cells generated inside mice. These structures are not only contain cells derived embryo development (of the three layers that make it up), but even outside the embryo tissue, such as the yolk sac.
addition, CNIO researchers detected stem cells in the bloodstream of mice treated
In both cases, both in the teratomas as in blood-derived stem cells showed some early embryonic stages further that the cells produced by the technique of Yamanaka. Ie had receded to a primitive level, so had a greater ability to differentiate into different cell types. Embryos had human features just 72 hours of gestation and 16 cells in the jargon are called totipotent traits.
These characteristics of differentiation as high “never been generated in the laboratory,” according to the authors. “These data indicate that our stem cells are much more versatile than Yamanaka iPS cells,” said Serrano.’s counterpart this power is that the cells are more difficult to control when it comes time to turn them into specific tissues.
purpose of regenerative medicine is to treat damaged organs through healthy cells. The raw material of this therapeutic approach are stem cells for their ability to become any of the 100 cell types. Specialists aspire to be able to manipulate these cells deprogrammed to turn them into healthy cells of liver, heart or pancreas which treat liver failure, stroke or diabetes. Or even develop entire organs in the lab parts to replace the sick.
iPS cells versatility meet these conditions. And besides, do not raise ethical issues if they have human embryonic stem cells. Therefore, CNIO researchers argue that the new source of stem cells that have been described may be a source alternative to those obtained in the laboratory for research in regenerative medicine. “Our stem cells survive well in cultures outside the mice,” said Maria Abad, first author of the article.
But there is another more attractive future therapeutic application, but whose application is much more remote. It would take advantage of the ability to create stem cells within the body to induce endogenous regeneration in an injured area.
natural processes of regeneration, target healthy cells repairing cells. In the study by Spanish researchers, explains Serrano, induced differentiation in adult cells was so high that the stem cells were insensitive to signals from the environment and developed teratomas.
One of the next targets CNIO researchers is whether there is a degree of differentiation that allows generated iPS stem cells interact with their environment and repair themselves, from within the injured tissue. “We will cause damage in mice, a stroke for example, and administer less medication, so that there is a lower degree of cellular reprogramming,” says the researcher. “We observe whether those less differentiated cells can give rise to cardiomyocytes that improve cardiac function.”
This change of concept, that of inducing therapeutic regeneration instead of creating replacement tissue in the lab, avoid risks of surgical interventions which should refer patients for organ and tissue repair. O handling accidents crops, among others.
Serrano’s group is not the first to raise this approach. A work of the Center for Regenerative Medicine in Barcelona and the Salk Institute
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