Grant Award Details
- Mural cells serve as a critical signaling hub of the neurovascular unit and have known roles in blood brain barrier formation.
- The experiments in this proposal will address a critical knowledge gap by defining the stages of mural stem cell development in the brain, understand mural stem cell identify and potential, and how each stage contributes to the blood brain barrier.
- Studies will also address the hypothesis that smooth muscle cells are evolutionarily conserved mural stem cells in the developing brain which give rise to classic pericytes, the differentiated effector cells of the blood-brain barrier.
Grant Application Details
- Harnessing vascular stem cells to grow and protect the human brain
The origins of brain vascular mural cells are unknown. This proposal will identify mural stem cells in the developing human and mouse brain and determine their impact on blood brain barrier formation.
Brain vascular diseases can have profound impacts on long-term neurological function. This proposal will map the stages of mural stem cells to protect these cells and harness them for regeneration.
Major Proposed Activities
- Determine the spatiotemporal dynamics of mural stem cells in the developing mouse and human brain.
- Determine the cellular potential of human and mouse smooth muscle cells versus pericytes in the developing mouse brain.
- Develop in vitro human neurovascular units (NVUs, organoids) to test the potential of human mural stem cells.
There are critical gaps in our understanding of blood vessel cells in the brain, which impact one of the most vulnerable patient populations. Preterm babies born before 30 gestational weeks are prone to develop brain hemorrhages. This condition affects approximately 12,000 babies a year in the United States, and survivors are prone to severe long-term neurological problems. This proposal will identify blood vessel stem cells to protect them and harness them for regeneration after injury.