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Effects of long-term nicotine exposure on stem cell therapy

Institution: Stanford University
Investigator(s): Alex Chan,
Award Cycle: 2019 (Cycle 30) Grant #: T30FT0860 Award: $207,300
Subject Area: Cardiovascular and Cerebrovascular Disease
Award Type: Postdoctoral Fellowship Awards

Initial Award Abstract
Cardiovascular disease is the leading cause of death worldwide. Among these diseases, peripheral artery disease (PAD) affects up to 8 million in the USA. It entails the loss of blood flow to limbs due to blocked arteries, ultimately leading to amputation if other treatment strategies are unsuccessful in restoring blood flow. A major risk factor for PAD is smoking, which leads to poorer prognosis than non-smoking PAD patients. A promising approach to treat PAD is stem cell therapy. Stem cells are cells which can transform into any cell type in the body. Stem cells can give rise to a wide range of cell types like endothelial cells that form new blood vessels through a process called angiogenesis. Among the most promising stem cell types are induced pluripotent stem cells (iPSCs). Human iPSCs are advantageous because they can be derived from a patient's own cells, thereby avoiding immune rejection. Consequently, iPSC derived endothelial cells (iPSC-ECs) offer a great potential in contributing to new blood vessels for diseased limbs. Although smoking is known to be extremely harmful and increases the risk of developing cardiovascular disease, the biological effects of the many components of tobacco smoking is unknown. Importantly, the effect of tobacco related metabolites exposure in patient-derived iPSC-ECs is largely unknown. Since tobacco usage can adversely affect the angiogenic actions of iPSC-ECs and thereby limit their efficacy as a therapy to restore blood flow, it remains critically important to understand how tobacco components interact with iPSC-ECs. In this proposal, the primary focus is on the effect of nicotine, the addictive component of tobacco, on iPSC-EC function. Nicotine is important because of its availability in a large range of tobacco related products, from cigarettes to chewing gum and patches to electronic cigarette liquid. The goals of the proposed project are to determine the effects nicotine exposure on the functionality of iPSC-ECs, how this process occurs biologically, and the development of a novel strategy to reverse the effects.