APR 11, 2024 8:00 AM PDT

Depleting Stem Cells Improves Immunity

Aging is a life process where the body slowly breaks down and becomes more vulnerable to external stimuli. For example, bones in older individuals become frail and muscle deteriorates. Additionally, older individuals are more susceptible to disease with a compromised immune system. In many cases there are protocols and guidelines in place to protect those with high susceptibility to disease. During the COVID-19 pandemic older patients had to be extremely careful to avoid contracting COVID-19.

Unfortunately, aging is a natural part of life. However, scientists are working to make the process of aging a little easier. Due to the increased average lifespan, aging has been a progressively growing field. Physicians and scientists are working to understand how we age and if there are secrets to be uncovered that would help avoid, prevent, or cure age-related diseases, such as cancer.

Stem cells are self-renewing cells in the body with the ability to differentiate into any cell type. The outcome to which final cell type it turns into is dependent on what the body needs. Regarding the immune system, the body generates more myeloid immune cells. Aging of the immune system is best characterized by an imbalance of these immune cells. Other immune cells including lymphoid cells related to adaptive immunity are reduced in number while myeloid cells and inflammatory pathologies are increased. Many believe that stem cells may be the cause of this imbalance.

A recent article in Nature, by Dr. Irving Weissman and his team, discovered that depleting myeloid stem cells rejuvenates or reinvigorates the immune system in aged mice. Dr. Weissman, the Virginia & D.H. Ludwig Professor of Clinical Investigation in Cancer Research at Stanford University, specializes in the generation of blood cells, leukemia, and stem cells made in the bone marrow. His work tries to understand the development of cells that make up the blood and immune system. In a young and healthy immune system, the lymphoid and myeloid cells are equally produced in number. This immune cell balance helps effectively combat infections entering the body. In this case lymphoid cells needed for the adaptive immune response limit increased myeloid cell development, which is highly inflammatory.

Due to the strong association between increased myeloid stem cells and aging, Weissman and his team went out to determine how critical this cell population is for the progression of aged immunity. Researchers went through different transcriptomic datasets to identify specific markers that characterize myeloid stem cells, including CD62p, NEO1, and CD150. Based on these markers, they then depleted myeloid stem cells in older mice using multiple depletion techniques. As a result, the researchers discovered that by depleting myeloid stem cells, the immune system was “revitalized” through increased immune cell production and activity. What is even more surprising is that when these older mice had depleted myeloid stem cells, they responded just as well to infection as younger mice with a healthy immune system.

Further investigation demonstrated that similar markers on this aged cell population can also be found in humans. However, more work needs to be done to improve the translational application of myeloid stem cell depletion. Overall, Weissman and his team discovered that myeloid stem cells age the immune system and prevent it from optimal function. This work has the potential to be applied in the clinic and given to older patients in combination with annual vaccines for enhanced immunity and protection.

Article, Nature, Irving Weissman, Stanford

About the Author
Master's (MA/MS/Other)
Greetings! I am a predoctoral trainee in the Department of Immunology at Roswell Park Comprehensive Cancer Center. I am passionate about tumor immunology, and hope to one day become an independent principal investigator.
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