A research carried out by Chilean scientists shows that administering stem cells in rats is effective to combat disorders related to alcohol consumption. The work, published Scientific Reports by researchers from the University of Chile and the University of Development (Universidad del Desarrollo), may lead to better therapies against alcoholism in humans.

Both rats and people who have drunk alcohol for a long time have problems with brain inflammation. So, their neurotransmitters change, reminding them how much they like to drink,” said Yedy Israel, reseracher at the Institute of Biomedical Sciences of the University of Chile.

When a human sees a bottle or smells alcohol, and when the rat is given some kind of information that there is alcohol present, as it can be also the smell, they want to drink again,” Israel added. However, mesenchymal stem cells, which in this work have been injected intravenously, have an anti-inflammatory effect, deactivating such cue-craving-reward mechanism.

A key factor for the success of this experiment was using Human Adipose Derived Stem Cells (ADSC) grown in 3D compared to the usual procedure. “If you put the cells in a petri dish they stick together, they spread out and result too large; but if you leave them floating in a liquid, they grow smaller,” Israel explained. That smaller size has allowed them to be injected into the blood and even cross the blood-brain barrier, similarly to white blood cells as they have the same size.

The experiments were carried out in rats that had been drinking alcohol for 17 weeks. The animals could also choose to drink tap water, but the animal model of alcoholism developed by the University of Chile after years of research has a slight preference for alcohol intake, specifically, vodka. A group of these rats was injected with a single dose of mesenchymal stem cells and within the next 24 hours they drank between 88 and 93% less alcohol than the animals that had not been given this treatment. The effect was observed even after three weeks.

In another trial, the authors of this study used rats that had been drinking alcohol for 14 weeks. They also injected a group with a dose of stem cells, but then restricted their alcohol intake for two weeks. After that time, the rats were given free access to alcohol for 60 minutes. The rats that had been treated consumed between 75 and 80% less. This second experiment allowed verifying that this therapy may also be effective to avoid relapses when it comes to abandoning alcohol.

Why do stem cells have this positive effect? “We know they produce anti-inflammatory cytokines, enzymes that reduce oxidative stress and are known as guardians of inflammation,” said Yedy Israel. “In reality, alcoholism, neuroinflammation and oxidative stress share the same mechanisms.” To understand these processes, the work on neuroinflammation by a team led by Consuelo Guerri, an expert from the Prince Felipe Research Center of Valencia (Spain), has been fundamental.

Fernando Ezquer, a scientist at the Center for Regenerative Medicine at the University of Development and first author of the article, believes that the results obtained in rats can be extrapolated to humans. “Currently, more than 1,200 people have been treated with stem cells in the world, always in the context of a clinical study, but in no case significant adverse effects have been reported. We observed in this work several safety markers of the animal and did not present any damage,” Ezquer said.

In addition, in the face of a possible development of a treatment for people with alcoholism problems, researchers are thinking about the possibility of not having to inject the ADSC, since they could directly administer the enzymes these cells produce. “The molecules they produce are responsible for the effect, which is very fast, and could be applied through non-invasive routes, for example, through the nose,” he said. Therefore, Chilean scientists are already working on the generation of a “much friendlier” biopharmaceutical, which could be presented as a nasal spray.

All this opens great possibilities, since the mechanism of neuroinflammation is not only caused by alcoholism, but is present in other addictions, for example, cocaine and nicotine; and in other diseases, including neurodegenerative pathologies. “This new biopharmaceutical could have extraordinary potential,” said Ezquer.

 

Source: Agencia ID