Hemangioblasts: From hematopoietic stem cells to endothelial progenitor cells and their effector molecules

Research in the field of stem cell has received much attention in the past few years. Stem cells hold tremendous potential for treating many debilitating conditions and diseases. My study describes how the hematopoietic stem cell is plastic, or capable of producing non-hematopoietic tissue in addition to all of the expected blood lineages. Specifically, the hematopoietic stem cell is capable of producing endothelial cells of blood vessels. I describe this through a series of experiments where I transplanted a single hematopoietic stem cell into a lethally irradiated recipient and reconstituted all of the blood lineages. This single cell was then able to produce endothelial cells under conditions of injury and ischemia in an attempt to relieve the ischemic pressure. I found that the hematopoietic stem cell can function as a hemangioblast, capable of producing not all of the blood lineages and also blood vessels. This activity suggests the possibility of modulating this hemangioblast activity.; I determined that two genes play a role in blood-pressure maintenance and immune responses in the Nitric Oxide Synthase pathway. These genes are also able to modulate hemangioblast function in mice. This ability to alter blood vessel formation would be extremely useful in conditions of pathologic blood vessel growth such as diabetic retinopathy, the leading cause of blindness worldwide, or tumor blood vessel growth where decreasing the blood supply could starve the cancer cells. Conversely, wound healing, and therapy for conditions such as stroke or cardiac ischemia, would benefit from increased blood vessel growth. This knowledge can be directly applied by using pharmacological agents that either inhibit or upregulate the Nitric Oxide Synthase genes to modulate blood vessel formation for therapies useful in human patients.