Restoring stem cells with antioxidants
Heshem Sadek, M.D., Ph.D., Assistant Professor of Internal Medicine, and Chengcheng “Alec” Zhang, Ph.D., Assistant Professor of Physiology and Developmental Biology at UT Southwestern Medical Center, share their latest research based on a new study about the critical role of the Meis1 gene in hematopoietic stem cells.
The study, published in the journal Blood, highlights the importance of oxygen metabolism in normal stem cell function and disease. In the future, these findings may have important implications for treating bone marrow failure and leukemia.
One of the most studied stem cells in adults is the blood stem cell, or hematopoietic stem cell. Although blood stem cells are very rare—they make up less than 0.01 percent of the bone marrow—they are essential in replenishing all blood cells throughout life.
Blood stem cells are usually highly efficient cells that work seamlessly to produce new blood cells; however, occasionally they malfunction and can cause leukemia, anemia, bleeding disorders, and lethal infections. Two important questions are how blood stem cells perform their functions throughout life and what goes wrong when they malfunction. To answer these questions, we determined how blood stem cells use oxygen. Unlike other cells, we found that blood stem cells are able to survive in the absence of oxygen.
We identified the Meis1 gene —which is known to be associated with aggressive leukemias—as a master regulator of oxygen in hematopoietic stem cells. We generated genetically modified mice in which the Meis1 gene was missing from hematopoietic stem cells and found that this loss causes the stem cell to use more oxygen than normal, thus leading to an increase in damaging oxygen free radicals.
The loss of the Meis1 gene also eliminated the ability of hematopoietic stem cells to replenish bone marrow, essentially eliminating their stem cell function. Interestingly, strong antioxidants completely restored the function of these genetically altered stem cells.