Human embryonic stem cells (hESC) provide a potentially unlimited source of oral mucosal tissues that may revolutionize the treatment of oral diseases. When fully exploited in the future, this source of cells will be able to produce functional tissues to treat a broad variety of oral diseases. However, little is known about how hESC can be developed into complex, multilayer oral tissues that line the gums, cheeks, lips, and other intra-oral sites. However, the use of hES cells for oral application faces numerous obstacles that must be overcome before their therapeutic potential can be realized.
Today, during the 87th General Session of the International Association for Dental Research, investigators from Tufts University in Boston report on their research to optimize the potential of hESC cells to generate complex, functional multilayer tissues, such as the oral mucosa and skin, and to understand how tissue fabrication is controlled and directed.
The Garlick lab has used tissue engineering principles to produce complex oral-lining tissues that mimic many features of their counterparts found in the oral cavity. Making these tissues was a two-step process. With a combination of chemical signals and specialized surfaces on which these cells attach, an hESC cell line (H9) was directed toward two divergent cell populations. The first population comprises the surface layer (epithelial cells) of complex tissues, while the other is found beneath these cells (mesenchymal cells). Following their isolation and characterization, the team incorporated these two distinct cell populations into the two tissue compartments that comprise these tissue types. The populations were then grown at an air-liquid interface to mimic their growth environment in the oral cavity. Within two weeks, tissues developed that shared many features in common with normal tissues that were constructed with mature cells that are the “gold standard” of normal tissue generation in our lab.
For the first time, researchers have established proof of concept that a single, common source of pluripotent hESC could provide the multiple cell types needed to be recombined within different, but interactive, tissue compartments to generate complex, multilayer tissues. In addition to providing oral mucosal tissues for future transplantation, the tissues generated in these studies can now be used to answer questions regarding the stability and safety of hESC-derived cells and tissues by providing information that will predict how they will respond after therapeutic transplantation in the future.