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Predicting bone teratogenicity of tobacco products in vitro

Institution: University of California, Riverside
Investigator(s): Ivann Martinez, B.Sc. Cell, Molecular Biology
Award Cycle: 2011 (Cycle 20) Grant #: 20DT-0038 Award: $59,825
Subject Area: General Biomedical Science
Award Type: Dissertation Awards

Initial Award Abstract
Tobacco use is the number one preventable cause of disease and death in the United States. Smoking cigarettes or consuming other tobacco products can lead to conditions that affect the heart and lungs, as well as cause cancer. There has been mounting evidence that tobacco products can affect the health of other organs or systems in the body, including the bone and the skeletal system. For example, the use of tobacco products has been suggested to increase the risks of osteoporosis and delayed bone healing in individuals that have undergone skeletal surgery. This is important because up until now most research that aims to determine the effects of tobacco products on the health of an adult person has mainly focused on its implication to health of the heart and lungs. Tobacco use can also result in complications regarding reproduction as well as aspects of development, for example the proper patterning of the embryonic skeleton. Thus, understanding the extent of the potency of tobacco products to cause skeletal birth defects is of pressing concern.

In the more recent decades, tobacco companies have acknowledged the fact that cigarette smoking may increase the risk of an individual to get cancer and have begun manufacturing and distributing modified tobacco products called harm reduction that contain less of the known carcinogens, such as tar and nicotine. Although these are advertized as safer alternatives to using conventional tobacco products, the truth behind the benefits of lowering risks to the unborn using these harm reduction types of tobacco products still remain untested.

In order to broaden our knowledge on the effects of tobacco products to embryonic growth and bone maturation, I am to develop a model that can accurately predict the effects of first and second hand smoke on all the stages of human embryonic bone development. As these studies would clearly be unethical to be conducted on early human embryos, I am proposing to use pluripotent stem cells as a cellular model, with which I can study development in a dish. Pluripotent stem cells are the most versatile among the stem cells and can generate all possible cell types of the adult body - among them bone forming cells. I believe that the use of these cells as a model to assess the ability of different tobacco products to interfere with normal bone formation will greatly contribute to understanding the relevance of harm-reduction products on human health.

The bone cells that form in vitro from these stem cells are remarkable to study and analyze as calcification in the dish is associated with a black coloration of the cultures. This typical appearance can be photographed or videos can be taken, so that image frames are analyzed using a novel image processing technique called videobioinformatics. Videobioinformatics will be useful in analyzing time-lapse images of bone formation in cultures that are treated with smoke from typical tobacco products dissolved in a solution in an automated manner. With videobioinformatics, I will be able to measure how stem cells specify into the bone cell lineage, when they stop dividing, how fast calcification occurs in culture and how strongly the cultures mineralize under influence of tobacco products. I will further compare the effects of conventional tobacco brands - mainstream smoke and second hand smoke - to various harm reduction tobacco products in all these endpoints. Using the videobioinformatics tool will allow me to establish the relative reduction of harm by the so-called harm-reduced variants of cigarettes.

This proposal aims to satisfy a key priority area of TRDRP to further study the effects of second hand smoke, especially those that are found in harm reduction tobacco products. The adaptation of a new method to study the changes in properties in the formation of bones from data obtained from a video can lead to a less labor intensive and more economical way to understand the effects of toxicants that are found in both first hand and second hand smoke.