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September 28, 2017

Doped mice cured of anemia

CiRA scientists show iPS cells can produce EPO to treat anemia in mice.

EPO (erythropoietin) has gained notoriety as the drug of choice in cycling. For anemia patients, however, EPO doping is essential, as it is the primary hormone responsible in the body for producing red blood cells. Patients with chronic kidney disease are especially susceptible to anemia, because the kidney is the primary site of EPO production. A new study by the Kenji Osafune laboratory shows iPS cells can be induced into cells that secrete EPO. The cells when transplanted convalesced anemic mice.

"Currently, the best treatment for anemia is recombinant EPO. But patients require treatment 1-3 times a week. We are looking for an EPO system that can reduce burden on the patient," says CiRA Professor Kenji Osafune, whose lab specializes in the study of kidney diseases using iPS cell technology.

To date, no cells that produce EPO (EPO cells) have been isolated from the kidney. Although EPO is produced by the kidney in adults, before birth, it is the liver that is responsible for its production. Therefore, the lab studied the genes in fetal liver essential for EPO production and developed ways to derive these cells from human iPS cells. It found the resulting EPO cells restored normal red blood cell count when transplanted into anemic mice

Additional study found that the number of EPO cells could be increased by treating the iPS cells with insulin-like growth factor 1 (IGF-1) and with prolyl hydroxylase domain-containing enzyme inhibitors, which regulate oxygen levels.

Osafune said that the discovery suggests these factors "could regulate EPO in the body and might reveal good targets for drug development to treat anemia."

Beyond new drugs, he also said that cell therapies through iPS cell research will bring new treatments and new understanding of how EPO cells are formed.

"Many mechanisms for EPO production have been found, but the details are not understood. That is why making EPO cells in the lab is so difficult. It is also difficult to isolate EPO cells from the body. iPS cells overcome these difficulties," he said.

Paper Details
  • Journal: Science Translational Medicine
  • Title: Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice
  • Authors: Hirofumi Hitomi1,2, Tomoko Kasahara1, Naoko Katagiri1, Azusa Hoshina1, Shin-Ichi Mae1, Maki Kotaka1, Takafumi Toyohara1, Asadur Rahman2, Daisuke Nakano2, Akira Niwa1, Megumu K. Saito1, Tatsutoshi Nakahata1, Akira Nishiyama2, Kenji Osafune1*

    *corresponding author
  • Author Affiliations:
    1. Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
    2. Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan
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