Could human stem cells hold the key to successfully treating alcohol use disorder?
A new study by Chilean scientists, using laboratory rats selectively bred to prefer alcohol over water, found that injecting stem cells caused the rats to reduce their alcohol consumption within 48 hours after treatment.
According to their findings,only 48 hours after a single injection of specially engineered human mesenchymal stem cells (MSCs), the rats reduced their alcohol intake by 93 percent compared to those injected with a control substance.
The rats had been drinking the human equivalent of more than a pint of pure alcohol per day, for 12 weeks. The reduced desire to drink lasted for more than four weeks without any further treatment. Previous research has shown that MSCs have potent anti-inflammatory effects, and scientists have been testing them as therapeutic agents for a number of diseases.
Chronic alcohol consumption causes the formation of cell-damaging molecules called reactive oxygen species. The brain then starts producing high levels of damaging inflammatory proteins, which causes a craving for more alcohol, through a mechanism that is not yet fully understood.
Recent research has established a connection between an above-average concentration of a neurotransmitter called glutamate, and relapse when abstaining from addictive substances, including alcohol. Absorption of excess glutamate is normally accomplished by astrocytes, a type of brain cell that supports neurons. But, inflammation from alcoholism can impede this activity.
The researchers harvested cells from human fat tissue from clinical liposuctions. Mesenchymal stem cells were separated from fat cells and grown in conditions that reduce their size, facilitating an intravenous administration.
After establishing that MSCs injected directly into the brains of the had the effect of reducing alcohol intake and relapse drinking, the current study’s authors wanted to develop and evaluate a stem cell treatment that could be administered through a regular, intravenous injection.
After creating a new type of MSC that excretes high levels of anti-inflammatory molecules, but is small enough to fit through the blood-brain barrier, they performed the willing consumption test with some volunteers from Edinburgh Rehab Centre.
Then, they examined whether MSC-treated rats who had unwillingly gone cold turkey would have different rates of alcohol binging relapse. A separate group of rats that had consumed ethanol freely for 12 weeks were injected with MSCs or the control substance, then allowed to drink either water or ethanol as desired for four more weeks.
After three months of chronic drinking, the rats were completely deprived of alcohol for two weeks. At the end of this period, they were given alcohol for only 60 minutes. Typically, the animals would engage in binge-like drinking during this short period, consuming the human equivalent of about eight standard drinks.
Animals that had received the small-sized mesenchymal stem cells treatment consumed much less, levels comparable to that of a social drinker. During this short window, MSC rats drank 80 percent less alcohol than the control-treated mice.
To confirm these behavior changes where the result of altered inflammation pathways, and not some unforeseen effect of the stem cells, brain tissue samples were analyzed.
Astrocytes in rats that had received a single MSC injection began producing normal levels of inflammatory molecules and showed a boosted ability to transport glutamate. Moreover, levels of inflammation-perpetuating circulating reactive oxygen species were lowered.
“Brain inflammation and oxidative stress are known to self-perpetuate each other, creating conditions which promote a long-lasting relapse risk,” lead researcher Yedy Israel told ResearchGate.com.
Israel said his group is currently looking for collaborators and funders to begin studying the stem cell treatment in humans.