Lab-Made 'Young' Immune Cells Partially Reverse Age-Related and Alzheimer-Like Brain Damage in Mice

Key finding: Researchers engineered 'young' mononuclear phagocytes from human induced pluripotent stem cells (iPSCs) and found that short-term treatment improved memory and certain markers of brain health in aged mice. The approach preserved microglia and mossy cells in the hippocampus and produced cognitive benefits, although many Alzheimer-related pathologies were not reversed.

What the study did

Scientists at Cedars-Sinai Medical Center generated replacement mononuclear phagocytes—immune scavenger cells—from human iPSCs. These cells ordinarily clear cellular waste and help limit inflammation, but they become less effective with age. The team injected lab-made, functionally "young" phagocytes into mice to test whether they could counteract age- and disease-related decline.

Main results

After treatment, naturally aged mice performed better on memory tests and showed signs of healthier brain immune cells. Specifically, treated animals displayed improved microglial profiles and a preserved population of mossy cells—neurons that support hippocampal function and are vulnerable to aging and Alzheimer's disease.

"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 biomedical scientist Clive Svendsen. "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."

How the benefits may occur

The injected engineered phagocytes did not appear to enter the brain, suggesting their effects were mediated indirectly. The researchers propose that circulating factors secreted by the fitter cells—such as anti-aging proteins or extracellular vesicles—traveled to the brain, reduced inflammation, and boosted local immune function.

Limitations and caveats

Most benefits were stronger in naturally aged mice than in genetically engineered mouse models of Alzheimer's disease. Crucially, much Alzheimer-related damage—such as amyloid-beta accumulation—was not reversed by the treatment. The authors caution that these promising preclinical results may not directly translate to humans.

"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," said Cedars-Sinai neuropathologist Jeffrey Golden, who was not directly involved in the study.

Implications

If developed further, autologous phagocytes derived from a patient's own iPSCs could reduce some risks associated with young plasma transfusions or bone marrow transplants and offer a more controllable cell-based therapy. Additional research is needed to identify the active circulating factors, confirm long-term benefits, and test safety and efficacy in humans.

Publication: The study appears in Advanced Science.