Scientists at Cedars-Sinai have developed “young” immune cells from human stem cells that reversed signs of aging and Alzheimer’s disease in the brains of laboratory mice, according to findings published in Advanced Science. The breakthrough suggests these cells could eventually lead to new treatments for age-related and neurodegenerative conditions in people.
Clive Svendsen, PhD, executive director of the Board of Governors Regenerative Medicine Institute and senior author of the study, explained the team’s innovative approach. “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,” Svendsen said. “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.”
Creating Youthful Immune Cells From Stem Cells
The cells, known as mononuclear phagocytes, normally circulate through the body to clear harmful substances. However, their function diminishes as organisms age. To produce youthful versions, researchers used human induced pluripotent stem cells — adult cells reprogrammed to an early embryonic-like state — to generate new, young mononuclear phagocytes.
When these lab-grown immune cells were infused into aging mice and mouse models of Alzheimer’s disease, the scientists observed remarkable improvements in brain function and structure.
Improved Memory and Brain Cell Health
Mice that received the young immune cells outperformed untreated mice on memory tests. Their brains also contained more “mossy cells” within the hippocampus, a region essential for learning and memory.
“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.”
In addition, the treated mice had healthier microglia — specialized immune cells in the brain responsible for detecting and clearing damaged tissue. Normally, microglia lose their long, thin branches as the brain ages or in Alzheimer’s disease, but in treated mice, these branches remained extended and active, suggesting preserved immune and cognitive function.
How the Treatment Might Work
The exact mechanism behind these benefits is not yet clear. Because the young mononuclear phagocytes did not appear to cross into the brain, researchers believe they may influence brain health indirectly.
The team proposes several possibilities: the cells could release antiaging proteins or tiny extracellular vesicles capable of entering the brain, or they might remove pro-aging factors from the bloodstream, protecting the brain from harmful effects. Ongoing studies aim to identify the precise mechanism and determine how best to translate these findings into human therapies.
Toward Personalized Anti-Aging 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.”
Additional authors include Luz Jovita Dimas-Harms, Rachel M. Lipman, Jake Inzalaco, Shaughn Bell, Michelle Alcantara, Erikha Valenzuela, George Lawless, Simion Kreimer, Sarah J. Parker,andHelen S. Goodridge.
Funding: This work was supported by the Universal Sunlight Foundation, the Cedars-Sinai Center for Translational Geroscience, and the Cedars-Sinai Board of Governors Regenerative Medicine Institute.
