In a preclinical study, immune cells derived from adult stem cells were shown to reverse signs of neurodegenerative changes in the brain.
“Young” immune cells developed by Cedars-Sinai researchers were able to reverse signs of aging and Alzheimer’s disease in the brains of mice, according to findings published in Advanced Science. These cells, generated from human stem cells, may one day provide the basis for new therapies to treat neurological disorders in people.
“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.”
Creating young immune cells
The cells in question, known as mononuclear phagocytes, normally travel through the body clearing harmful material, though their effectiveness declines with age.
To generate younger versions of these cells, the team reprogrammed human adult cells into induced pluripotent stem cells, which can be reset to an early embryonic state. From these, they produced new mononuclear phagocytes and infused them into aged mice and mice with Alzheimer’s-like disease.
Mice given the young cells performed significantly better on memory assessments compared with untreated mice. They also retained higher numbers of “mossy cells” in the hippocampus, a brain structure essential for learning and memory.
Effects on brain health
“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.”
Mice receiving the young mononuclear phagocytes also had healthier immune cells, called microglia, in their brains. These microglia use long, thin branches to detect and clear debris and damaged cells. The branches shrink and retract due to aging and Alzheimer’s disease, but they remained long and healthy in mice receiving the therapy.
Possible protective mechanisms
The mechanism behind the effects in the brain remains to be established. As the young mononuclear phagocytes did not appear to enter the brain, investigators believe the cells may have worked indirectly.
The cells could have released antiaging proteins or even tiny particles called extracellular vesicles, which are small enough to enter the brain. Or they could have absorbed pro-aging factors from the blood to keep them out of the brain. The mechanism of protection is the focus of ongoing studies to determine the most effective way to turn these findings into a therapy that could be used in a clinical trial in patients.
“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.”
Reference: “Human iPSC-Derived Mononuclear Phagocytes Improve Cognition and Neural Health across Multiple Mouse Models of Aging and Alzheimer’s Disease” by V. Alexandra Moser, Luz Jovita Dimas-Harms, Rachel M. Lipman, Jake Inzalaco, Shaughn Bell, Michelle Alcantara, Erikha Valenzuela, George Lawless, Simion Kreimer, Sarah J. Parker, Helen S. Goodridge and Clive N. Svendsen, 24 August 2025, Advanced Science.
DOI: 10.1002/advs.202417848
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.
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