Scientists have given mice stem cell transplants and saw a decrease in the brain abnormalities associated with Alzheimer’s disease.
The team, led by Stanford University scientists in the US, used blood stem and progenitor cells to transplant into mice, replacing the microglia, a kind of brain cell that is damaged in diseased mice.
“This cell therapy approach is unique in the field because most researchers are working to find pills or injectables to treat Alzheimer’s disease,” said Marius Wernig, a professor of pathology at Stanford.
In August, the findings were released in the journal Cell Stem Cell.
Even though Alzheimer’s has been the subject of much research, its causes and progression remain poorly understood.
Although it is unclear whether amyloid plaques in the brains of persons with Alzheimer’s disease are only an indication of the illness’s pathology or are the actual cause of dementia, most medications concentrate on removing the buildup of these plaques.
However, there is a definite link between different microglial mutations and nonfamilial Alzheimer’s disease, which typically manifests later in life and is not caused by an inherited gene variant.
In addition to acting as a defense mechanism for other brain cells against invaders, microglia cells also clear up the metabolic waste that can build up in the brain.
Some genetic variants in microglia have been found to strongly correlate with an increased risk of Alzheimer’s disease, according to scientists.
One such association includes the gene TREM2, which is crucial for how microglia recognize and respond to neurodegeneration.
“Certain genetic variants of TREM2 are among the strongest genetic risk factors for Alzheimer’s disease,” Wernig said.
“The data are convincing that microglial dysfunction can cause neurodegeneration in the brain, so it makes sense that restoring defective microglial function might be a way to fight neurodegeneration in Alzheimer’s disease,” he added.
In the study, hematopoietic stem and progenitor cells from mice with healthy TREM2 function were transplanted into animals with a faulty TREM2 gene.
The transplanted cells quickly rebuilt the circulatory system, and some of them transformed into cells that resembled microglia in appearance and behavior when they successfully merged into the recipients’ brains.
“We showed that most of the brain’s original microglia were replaced by healthy cells, which led to a restoration of normal TREM2 activity,” Wernig said.
The next step was to determine whether the TREM2-deficient mice’s brain health could be improved by the restored TREM2 activity.
“Indeed, in the transplanted mice we saw a clear reduction in the deposits of amyloid plaques normally seen in TREM2-deficient mice,” Wernig said.
Additionally, they were able to demonstrate the restoration of microglial function and a decrease in other disease markers, proving that the functional restoration of just one gene had beneficial benefits across the board.
The transplantation of cells with enhanced TREM2 activity, according to the researchers, could have an even bigger impact.
However, they do note that the microglia that developed from the transplanted cells differed slightly from the native microglia in mouse brains.
“These differences might in some way have their own detrimental effect. We have to look at that very carefully,” Wernig said.
The transplant of blood stem cells necessitates the recipient to undergo a highly toxic chemotherapy or radiation treatment in order to eradicate native blood stem cells, which the researchers observed makes the current approach extremely dangerous if it were adapted for human therapy.
Many scientists are working on less harmful approaches of preparing patients for stem cell transplants, nevertheless. They suggested that a brain cell therapy may then build on such enhanced and safer transplanting techniques.