To get life-giving oxygen into every cell, the human body produces two to three million oxygen-carrying red blood cells each second, a process controlled by the hormone erythropoietin (EPO), which works by binding to cells in the bone marrow and promoting their proliferation. Discovered decades ago, the identity of the cells that make this hormone remained unknown – until now.
In a new paper, published in Nature Medicine, Weizmann scientists from Prof. Ido Amit’s lab and colleagues from Israel, Europe, and the United States have identified a rare subset of kidney cells that are the main producers of EPO in the human body, a discovery that has transformative potential for patients with anemia.
EPO is probably most famous – or infamous – for its illegal use as a doping agent in sports, most notably by the cyclist Lance Armstrong, who took a synthetic version. But the hormone’s therapeutic potential goes far beyond enhancing stamina, and it has fascinated researchers for more than a century.
More than 10 percent of the population have chronic kidney diseases that often impair EPO production, which occurs mainly in the kidneys. The resulting anemia can, in severe cases, be lethal. Until recently, the only way to treat people with this type of anemia was with EPO produced by DNA technology. This discovery may shed new light on the functioning of existing EPO medications and help scientists develop new ones.
A world leader and pioneer in the fields of single-cell genomics and clinical big-data analytics, Prof. Amit of the Weizmann Institute’s Department of Systems Immunology believes that the identification of these cells in the present study may have an impact rivaling that of the discovery of insulin-producing beta cells in the 1950s. Finding the cells that produce EPO lagged behind because, unlike insulin and other major protein hormones, EPO is not stored in the cells; rather, it is rapidly produced and released in response to a lack of oxygen.
In the present study, the researchers managed to identify these cells by using the sophisticated technologies developed in Prof. Amit’s lab. These include advanced techniques for single-cell analysis that enable the study of tens of thousands of individual cells simultaneously and thus the identification of rare types of cells in tissues.
Dr. Barak Rosenzweig, a senior urologic oncologist in the Department of Urology at Sheba Medical Center in Israel who participated in the study, explains that the discovery of these cells has important clinical potential, not only for patients with chronic kidney disease, but for those with other conditions as well. For instance, many cancer patients receive blood infusions to boost their red blood cell count before surgery. However, these infusions can negatively affect the immune system, hindering the patients’ ability to fight the cancer in the long run.
This discovery “presents the opportunity to develop techniques that would stimulate these cells to produce more EPO, enhancing a patient’s blood count without affecting the immune system,” Dr. Rosenzweig explains. “That’s a prime example of the significance of basic science, which can uncover previously unknown pathways and lay the groundwork for creating new therapies, particularly when current clinical solutions are insufficient.”