A study recently published in Advanced Science from Cedars-Sinai reports the development of young immune cells from human stem cells that reversed the signs of aging-related cognitive decline and Alzheimer’s disease in the brains of laboratory mice. The findings describe the treated animals exhibiting better memory and healthier brain structures, with the cells appearing to protect the brain indirectly, which is thought to be through anti-aging signals in the blood, suggesting a new personalized path to slowing brain aging and neurodegenerative conditions.
“Previous studies have shown that transfusions of blood or plasma from young mice improved cognitive decline in older mice, but that is difficult to translate into a therapy,” said Clive Svendsen, PhD, executive director of the Board of Governors Regenerative Medicine Institute and senior author of the study. “Our approach was to use young immune cells that we can manufacture in the lab — and we found that they have beneficial effects in both aging mice and mouse models of Alzheimer’s disease.”
Using Stem Cells to Create Youthful Immune Cells
The youthful immune cells are known as mononuclear phagocytes, which typically circulate around the body, helping to clear harmful substances. However, the function of mononuclear phagocytes diminishes with age.
To produce more youthful versions of these cells, human induced pluripotent stem cells were used to generate the new and younger mononuclear phagocyte cells. When the younger immune cells were infused into aging mice and models of Alzheimer’s disease, the animals were observed to exhibit remarkable improvements in both their brain structure and function.
Remarkable Improvements
The treated animals were observed to outperform the untreated animals on memory testing, and their brains contained more “mossy cells” within the hippocampus region, which is essential for memory and learning.
The treated animals were also found to have healthier specialized immune cells in their brains called microglia that are responsible for detecting and clearing damaged tissues. As the brain ages or with Alzheimer’s disease, microglia will typically lose their long and thin branches; however, in the treated animals, the branches remained active and extended, which suggests preserved immune and cognitive function.
“The numbers of mossy cells decline with aging and Alzheimer’s disease,” said Alexendra Moser, PhD, a project scientist in the Svendsen Lab and lead author of the study. “We did not see that decline in mice receiving young mononuclear phagocytes, and we believe this may be responsible for some of the memory improvements that we observed.”
Another Step Towards Personalized Anti-Aging Therapies
While the mechanisms behind these remarkable improvements are not yet completely clear, it is thought that because the young mononuclear phagocytes did not appear to cross into the brain, researchers believe they may influence brain health indirectly.
The researchers propose different possibilities: the cells could be releasing antiaging proteins or tiny extracellular vesicles that are capable of entering the brain, or they might remove pro-aging factors from the bloodstream, protecting the brain from harmful effects.
The researcher’s ongoing stem cell research will be aimed at identifying the precise mechanisms and determining how best to translate these findings into human therapies.
“Because these young immune cells are created from stem cells, they could be used as personalized therapy with unlimited availability,” said Jeffrey A. Golden, MD, executive vice dean for Education and Research. “These findings show that short-term treatment improved cognition and brain health, making them a promising candidate to address age- and Alzheimer’s disease-related cognitive decline.”
This article was written at the WHN News Desk.
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