(Newswise) — LOS ANGELES — “Young” immune cells created by Cedars-Sinai investigators reversed signs of aging and Alzheimer’s disease in the brains of laboratory mice, according to a study published in the journal Advanced Science. The immune cells, which were produced from human stem cells, could be used to develop new treatments for neurological conditions in humans.
“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.”
The immune cells, called mononuclear phagocytes, circulate throughout the body disposing of harmful substances, but become less effective as we age.
The investigators used human induced pluripotent stem cells, which are adult cells that have been taken “back in time” to an early embryonic state, to generate young mononuclear phagocytes. When the young cells were infused into aging mice or a mouse model of Alzheimer’s disease, investigators noted several important changes.
First, the mice receiving the young cells performed better on memory tests than mice without cell treatment. These mice were also found to have more “mossy cells” in the hippocampus, a brain region critical 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.”
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.
The mechanism behind the effects in the brain remain 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.”
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, and Helen 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.
