Cardiovascular diseases are a leading cause of death in California and the United States. It is generally accepted that vascular diseases such as atherosclerosis and restenosis are caused by the dysfunction of endothelial cells (ECs), inflammatory responses, and the de-differentiation and proliferation of smooth muscle cells (SMCs). However, our recent findings suggest that the activation and differentiation of a novel type of vascular stem cells (VSCs) in the blood vessel wall rather than the de-differentiation of SMCs result in the proliferative/synthetic SMCs in neointima, suggesting that vascular diseases are stem cell diseases. In addition, VSCs can be identified and isolated in atherosclerotic lesions of human coronary arteries, but the role of human VSCs in the development of vascular diseases remains to be elucidated. We propose to use a tissue engineering approach to reconstitute an in vitro three-dimensional (3D) model of human vascular diseases based on our findings on VSCs. This human VSC-based in vitro 3D model will not only shed light on the microenvironmental regulation of VSC activation and differentiation, but also provide an enabling technology for high throughput screening of new drugs by targeting VSCs for the therapies.
Statement of Benefit to California:
Cardiovascular diseases are a leading cause of death in California, in the United States and in the world. In the past few decades, the therapies have been developed to target smooth muscle cells in the blood vessels. Here we propose a new stem cell model of vascular diseases and suggest that vascular stem cells rather than smooth muscle cells play an important role in disease development and thus vascular stem cells should be the target of therapies. The results of this project will have transformative impact on the development of novel therapies for vascular diseases, and will benefit the health care in California and beyond. This 3D in vitro model of vascular diseases will not only be valuable for the investigation of the disease mechanisms but also be a enabling technology for the high throughput screening of new drugs for therapies.