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Valine deficiency will deplete hematopoietic stem cells

Jun 21, 2021

In a new study, researchers from the Stanford University School of Medicine in the United States and the University of Tokyo in Japan found that a diet that depletes hematopoietic stem cells may make bone marrow transplantation feasible without chemotherapy or radiotherapy.

The researchers demonstrated that a diet lacking the essential amino acid valine can effectively deplete the hematopoietic stem cell population in mice, allowing these mice to successfully receive hematopoietic stem cell transplants from other mice. They also confirmed in the laboratory that artificial blood stem cells are affected by valine deficiency, which suggests that the same treatment may also be effective in humans.

The relevant research results were published online on October 20, 2016 in the journal Science, with the title of the paper "Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation". The first author of the paper is Yuki Taya, a former graduate student of the University of Tokyo. The corresponding authors of the paper are Dr. Hiromitsu Nakauchi, professor of genetics at Stanford University School of Medicine, and Dr. Satoshi Yamazaki, associate professor of the Center for Stem Cell Biology and Regenerative Medicine, University of Tokyo.

Efficacy of a valine-deficient diet

Nakauchi said, "Bone marrow transplantation is a treatment with toxic side effects. We have to do this to treat fatal diseases, but the quality of life after treatment is often not so good."

He added, "Compared to chemotherapy or radiotherapy, the toxicity of a valine-deficient diet seems to be much lower. The mice that received radiotherapy looked worse. They were unable to become pregnant and survived for less than a year. However, they were fed with a lack of valine. Mice on the amino acid diet can become pregnant and have a normal life span after receiving the transplant."

Nakauchi said that the efficacy of a valine-deficient diet is specific to hematopoietic stem cells, but it seems that other types of stem cells may also be affected, such as hair follicle stem cells and some T cells. He said that although other types of stem cells may also be affected, these effects are not as widespread or severe as those caused by chemotherapy or radiotherapy.

Nakauchi is particularly interested in a type of stem cell that may be affected by valine deficiency. Nakauchi said that if leukemia stem cells are also sensitive to valine deficiency, then it may open the door to the development of a diet therapy for these blood cancers.

In this new study, Yamazaki, Nakauchi and their colleagues tested the effect of the presence or absence of specific amino acids on hematopoietic stem cells. They found that the lack of valine or another amino acid, cysteine, in the laboratory dishes makes the growth of mouse hematopoietic stem cells impossible.

Subsequently, the researchers constructed a mouse food lacking only these specific amino acids and fed the food to the mice for 4 weeks. They found that a diet lacking valine rather than a diet lacking cysteine depleted the hematopoietic stem cells in these mice.

Nakauchi said, "Unlike valine, cysteine is not an essential amino acid, which means that the body can make some cysteine. However, all the valine we need comes from our diet."

Valine


The current dietary method complements other studies recently reported by Stanford University scientists that use antibodies instead of chemotherapy or radiotherapy to remove hematopoietic stem cells in preparation for bone marrow transplantation. Nakauchi said, "These two methods may even be used together to provide a more effective and gentler treatment."

He said that the mechanism by which amino acid deficiency affects hematopoietic stem cells is unknown, but this will be the focus of future research. Given that this amino acid is expected to become the basis of a diet therapy, Nakauchi believes that scientists may find that other specific types of stem cells are affected by the presence or absence of specific amino acids. He said, "This research may open the door to a new field of stem cell metabolism and become the basis for a series of diet therapies."


He added, “It also emphasizes the importance of a comprehensive diet to keep all our cells healthy.”