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Metabolism found to regulate production of killer cells

Published 12 April 2022
istock/selvanegra
istock/selvanegra

In a recent study from Lund University in Sweden, researchers discovered that metabolic changes affect how blood cells are formed during embryonic development. They found a previously unknown metabolic switch with a key role in how different types of blood cells develop. This means blood cell formation can be directed towards producing natural killer cells in the laboratory to ultimately be used in a new anti-cancer treatment.

Around two billion natural killer cells circulate in our bodies and play an important role in the body's defense against cancer and infection. This has led researchers to believe that natural killer cells can be used in immunotherapy treatment for those same illnesses. Therefore, we need to understand how these anti-cancer cells are first produced from blood stem cells originating in the embryo.

“By taking cells from an adult's tissue - for example a hair follicle or a skin cell - we can reprogram them to an embryonic-like state - so-called iPS cells, induced pluripotent stem cells. Because of the embryonic state, these cells can then develop into different cell types of the body, including blood cells”, says Niels-Bjarne Woods, Associate Professor at Lund University and a corresponding author of the study.

In our system to generate blood cells from iPS cells, the research team found a metabolic switch that can activate the generation of specific blood cell types, and consequently increase the production of natural killer cells.

Photo of Leal Oburoglu and Niels-Bjarne Woods
Leal Oburoglu, first and co-corresponding author, and Niels-Bjarne Woods, senior and co-corresponding author, on the EMBO Reports research article.

“In our cells there are mitochondria that function as power plants, where chemical reactions deliver energy for the cells. By feeding the cells differing substances we could impact the energy production and influence which types of blood cells were developed. We performed the studies in the lab first, and then confirmed the result in animals, achieving similar results”, says Niels-Bjarne Woods.

Increased activity in the mitochondria resulted in substantially higher levels of natural killer cells. This shows that metabolism is an important regulator of blood development during the embryonic stage.

“Using metabolic factors, we identified how to control the production of specific blood cells from iPS cells. Weplan to modify the natural killer cells to target and destroy specific cancers. Transplanting genetically modified natural killer cells from iPS cells is the next big hope for anti-cancer therapies”, concludes Niels-Bjarne Woods.“We just made producing natural killer cells more on-demand.”

Publication:

Link to the article in EMBO Reports:

Pyruvate metabolism guides definitive lineage specification during hematopoietic emergence

 

Link to original article published on 9 February 2022

 

Funding

The study has been funded with the support of the Wenner-Gren Foundations, EMBO Long-term fellowship, BioCARE, Knut and Alice Wallenbergs Foundation, the Swedish Childhood Cancer Fund, the Swedish Research Council, the Swedish Cancer Society, the Royal Physiographic Society of Lund, the Swedish Society for Medical Research.

Declaration of interests

Niels-Bjarne Woods is the founder and shareholder of Amniotics AB, Lund, Sweden, a research company that develops cell therapy drugs based on mesenchymal stem cells. The company is interested in developing the technology from this study for the clinical application of using killer cells for cancer treatment.

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12 Apr 2022