Ovol genes and hES differentiation into hair-producing cells
Each year in America, there are 700,000 emergency visits and 45,000 hospitalizations for burn treatments, and 4,500 deaths due to fire and burns (http://www.ameriburn.org/resources_factsheet.php). Since twenty years ago, the use of artificial skin generated from human skin cells has tremendously improved the survival rate of severely burned patients. However, this technology suffers a major drawback: the artificial skin lacks the various structures that are part of the normal skin, such as hair follicles, sweat glands, and cells that make pigments or fight pathogens. Embryonic stem cells are cells that are isolated from early embryos and have the potential to make all kinds of cells in the human body. Conceivably, they hold great promises to help generate a new kind of artificial skin containing all residential structures and cell types that would function just like real skin.
Hair follicles play many important roles in skin – they provide a passage for perspiration, are the source of cells that are used for natural wound repair, and the house of other important cell types. We therefore will focus our effort to first use hES cells to make hair follicle-containing skin on Petri dishes. Theoretically, a hES cell has to make three important, sequential fate choices during its path to become a hair follicle cell. First, it has to choose a fate that has the potential to be part of the nervous system or part of skin. After this, it has to then choose a skin fate over a neural fate. Last, it has to choose to become a hair follicle cell instead of just the skin between follicles. We will experimentally manipulate these fate choices by adding or removing key regulatory proteins (such as growth factors) that are known to be involved in these decisions based on studies in model systems such as mice. Clearly, this is a long-term process: we not only have to find conditions that would allow the generation of some hair-producing cells, but also have to optimize the conditions so that we can generate many of such cells and have them distribute in a pattern that resembles the distribution of hair follicles in normal skin. Our goal in the current grant application is to be able to generate some hair-producing cells from hES cells. This, if successful, will lay the ground for future work from our as well as other laboratories. Ultimately, we may be able to generate hair follicle-containing skin to be used for transplantation not only onto burn patients, but also onto healthy people with baldness.
Wildfire has been an unfortunately frequent presence in the State of California. As the state continues to grow, more and more people live in forest areas, facing a high risk of physical (and property) damage from wildfire. For example, a total of 3500 houses were burned in the Oakland/Berkeley fire in 1988 and Painted Cave fire in 1990. This, together with other causes of fire and burn such as use of defective product and accidents, leaves Californian citizens suffering from a high incidence of burns and injuries. The studies we propose in this application may yield findings that will directly benefit the health and welfare of burn patients in California. Furthermore, these findings may also be used to help establish industrial entities in the State of California that perform research, development, and marketing of new therapeutic products. This will create new job opportunities for California citizens and increase revenues for the State of California.