A study at the University of California San Diego (USA) showed that hematopoietic stem cell transplantation can protect against memory loss, neuroinflammation, and B-amyloid accumulation in mice with Alzheimer’s disease. Stem cell therapy is already being used to treat various types of cancer and diseases of the blood and immune system. In this new study, published in the scientific journal Cell Reports, hematopoietic stem and progenitor cell transplantation was found to be effective in rescuing multiple signs and symptoms of Alzheimer’s disease in a mouse model of the disease. Mice injected with healthy hematopoietic stem cells showed preserved memory and cognitive function, reduced neuroinflammation, and significantly less accumulation of amyloid-B compared to other mice with Alzheimer’s disease. “Alzheimer’s disease is a very complex disease, so any potential treatment would need to target multiple biological pathways.” Our work demonstrates that hematopoietic stem and progenitor cell transplantation can prevent complications of Alzheimer’s disease and may be a promising therapeutic route for this disease. Alzheimer’s disease,” says study lead author Stephanie Cherky. The success of the therapy lies in its effect on microglia, a type of immune cell in the brain. Microglia are involved in various ways in the onset and progression of Alzheimer’s disease. It is known that persistent inflammation of microglia may contribute to the development of Alzheimer’s disease, since the release of inflammatory cytokines, chemokines and complement proteins leads to an increase in the production of B-amyloid. In healthy microglia, microglia also play an important role in the removal of B-amyloid plaques. , but this function is impaired in Alzheimer’s disease. The subsequent accumulation of B-amyloid also puts pressure on other brain cells such as endothelial cells, affecting blood flow to the brain. The researchers wanted to see if a stem cell transplant could create healthy new microglia that would slow the progression of Alzheimer’s disease. This group of scientists has previously had success with similar stem cell transplants to treat mouse models of cystinosis, lysosomal storage disease, and Friedreich’s ataxia, a neurodegenerative disease. They performed systemic transplantation of healthy hematopoietic stem cells and wild-type progenitor cells into mice with Alzheimer’s disease and found that the transplanted cells differentiate into microglia-like cells in the brain. They then assessed the behavior of the animals and found that memory loss and neurocognitive impairment were completely prevented in mice that received stem cell transplants. These mice showed improved object recognition and risk perception as well as normal levels of anxiety and locomotor activity compared to untreated mice. By closely examining the brains of the animals, the researchers found that mice given healthy stem cells experienced a significant reduction in B-amyloid plaques in the hippocampus and cerebral cortex. The transplant also reduced microgliosis and neuroinflammation and helped maintain the integrity of the blood-brain barrier. Finally, the researchers used transcriptome analysis to measure the expression of various genes in treated and untreated mice with Alzheimer’s disease. Those who received stem cell therapy had less cortical expression of genes associated with diseased microglia and less expression of genes associated with diseased endothelial cells in the hippocampus. Taken together, transplantation of healthy hematopoietic progenitors and stem cells improved microglial health, which in turn protected against multiple levels of Alzheimer’s pathology. A third group of mice injected with stem cells isolated from Alzheimer’s mice showed no signs of improvement, demonstrating that these cells retained information related to Alzheimer’s disease. Future research will continue to explore how transplanted healthy cells lead to such dramatic improvements, and whether similar transplant strategies can be used to alleviate Alzheimer’s symptoms in humans.
July 23, 2023