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The ability of our hematopoietic stem cells (HSCs) to generate new red and white blood cells as well as other essential blood components declines with age, which can lead to chronic inflammation, expedite the formation of blood malignancies, and accelerate degenerative diseases.
By lowering the iron levels in these adult stem cells, researchers from Albert Einstein College of Medicine and the Montefiore Einstein Comprehensive Cancer Center (MECCC), recognized by the National Cancer Institute, have discovered a way to stop or even reverse failed HSC function. The journal Cell Stem Cell publishes the findings.
Britta Will, Ph.D., an associate professor of oncology, medicine, and cell biology at Einstein, the Belfer Scholar in Cancer Research, and co-leader of the stem cell & cancer biology program at MECCC, said that this decline in HSC function is avoidable and seems to be reversible.
Through the use of a clinically accessible medication to reduce iron levels within the cell, the researchers were able to recover the young HSC pool in aged mice. This simple therapeutic approach may be able to reduce blood malignancies, chronic inflammatory diseases, and age-related illnesses.
This study began in 2018 when Dr. Will and colleagues noticed that eltrombopag, a medication intended to increase platelet counts, also boosts HSC activity. At that point, the researchers found that eltrombopag chelates iron from HSCs, which is why this enhancement happens. Their most recent findings demonstrated that the amount of iron in HSCs determines their fate and function.
After studying HSCs, the researchers discovered that too much intracellular iron causes inflammation in the cells and drives them into dormancy, a state characterized by drastically reduced cell activity that is comparable to animal hibernation. Dormancy reduces HSCs’ capacity to proliferate and generate an adequate amount of high-grade red blood cells. Conversely, HSCs with low iron levels multiply swiftly and perform well in situations requiring more blood components.
How can iron restriction preserve the health of HSCs? Researchers have discovered that low iron causes HSCs to temporarily boost their metabolism of fatty acids, reinforcing their genetic programming after they have multiplied in young mice. On the other hand, it was shown that the HSC of aged mice had greater iron levels, which inhibited the activation of this newly discovered fatty-acid metabolic pathway.
The researchers then looked at whether or not removing iron from HSCs would increase the production of blood cells in older and aging mice. They injected the iron chelator deferoxamine daily into aged mice for a period of 14 days in order to lower the iron levels in HSCs.
After their HSCs were transplanted into other mice, aged HSCs subjected to iron chelation produced an enormous rise in blood cells in comparison to controls. Extended iron chelation produced even more noticeable results. Middle-aged mice administered with iron chelator for 13 more months had HSCs that were up to 10 times more capable of regenerating than those of controls.
Source:
Yun-Ruei Kao et al. (2024). An iron rheostat controls hematopoietic stem cell fate, Cell Stem Cell. DOI: 10.1016/j.stem.2024.01.011
Iron Restriction Keeps Blood Stem Cells Young | Newsroom | Albert Einstein College of Medicine (einsteinmed.edu)
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