Cedars-Sinai scientists have developed “rejuvenating” immune cells from human stem cells that reverse signs of aging and Alzheimer’s disease in the brains of laboratory mice. Advanced science. The breakthrough suggests these cells could eventually lead to new treatments for age-related and neurodegenerative conditions in people.
Clive Swedson, Ph.D., 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 old mice, but translating this into therapy has been difficult,” Swedson said. “Our approach was to use young immune cells that we could generate in the lab — and we found that they had beneficial effects in both aging mice and mouse models of Alzheimer’s disease.”
Generation of juvenile immune cells from stem cells
The cells, known as mononuclear phagocytes, normally circulate through the body to clean up harmful substances. However, their function decreases as the organism ages. To develop the adult version, the researchers used human induced pluripotent stem cells—adult cells reprogrammed to an early embryonic-like state—to produce new, young mononuclear phagocytes.
When lab-grown immune cells were added to aging mice and mouse models of Alzheimer’s disease, scientists observed significant 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 “mushy cells” within the hippocampus, a region important for learning and memory.
“The number of rogue cells decreases with aging and Alzheimer’s disease,” said Alexandra Moser, a project scientist in the Swedson lab and lead author of the study. “We didn’t see this reduction in mice acquiring young mononuclear phagocytes, and we believe that this may be responsible for some of the memory improvements we observed.”
In addition, the treated mice had healthier microglia — specialized immune cells in the brain that are responsible for detecting and cleaning up damaged tissue. Normally, microglia lose their long, thin branches in brain aging or Alzheimer’s disease, but in the treated mice, these branches remained expanded and active, suggesting protected immune and cognitive function.
How can treatment work?
The exact mechanism behind these benefits is not yet clear. Because young mononuclear phagocytes did not appear to enter the brain, researchers believe they may indirectly influence brain health.
The team suggests several possibilities: the cells could release antigenic proteins or tiny cell-associated vesicles capable of entering the brain, or they could remove aging factors from the bloodstream, protecting the brain from harmful effects. Ongoing studies are aimed at identifying the exact mechanism and determining how best to translate these findings into human treatment.
Towards anti-aging therapies
“Because these young immune cells are made from stem cells, they can 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 improves cognition and mental health, making them a promising candidate for treating age-related and Alzheimer’s disease-related cognitive decline.”
Additional authors include Luz Jovita Demas Harms, Rachel M. Lipman, Jack Anzalco, Shawn Bell, Michelle Alcantara, Erica Valenzuela, George Niz, Samian Kramer, Sarah J. Parker, 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 of the Regenerative Medicine Institute.
