Hydrogen Sulfide Induces Dental Pulp Stem Cells to Become Liver Cells

The gas hydrogen sulfide smells like rotten eggs, and it is also poisonous in high quantities. It is produced throughout the body, and the exact role of it is unknown. However, scientists from the Nippon Dental University in the laboratory of Ken Yaegaki have shown that small quantities of this gas can induce particular adult stem cells to differentiate into liver cells.

Human teeth contain several stem cell populations, and one of these, the dental pulp stem cells, can make liver cells with remarkable efficiency. Dental pulp is composed of connective tissue and cells and dental pulp stem cells can be obtained from teeth after extraction.

Human tooth pulp stem cells contain a subpopulation that possesses a particular cell surface molecule called “CD117,” which is also known as the mast/stem cell growth factor receptor.  Those cells with this surface protein were isolated from the rest of the stem cells.  They then grew these stem cells in culture, and transferred them to a culture medium that contained a basic nutrient medium (Dulbecco’s modified Eagle’s medium for those who might be interested) and added to that medium, insulin, an iron-binding protein called transferrin, and two growth factors (embryotrophic factor and hepatocyte growth factor) for five days. Then they transferred the cells to another medium that was similar to the previous medium, but also had a cytokine called “oncostatin” and a steroid drug called dexamethasone for 15 days.  The atmosphere for these cells included either 5% carbon dioxide, and no or a small amount of hydrogen sulfide (0.05 ng ml−1).

After growing cells under these conditions, those cells that had been grown in the presence of hydrogen sulfide were more liver-like when it came to their biochemistry.  Liver cells store large amounts of sugar in the form of glycogen, produce a waste product called urea as a result of a pathway called the urea cycle, and make a large cadre of enzymes and proteins that are specific to the liver.  In almost every case, the cells grown in the presence of hydrogen sulfide made more liver-specific proteins than those grown without hydrogen sulfide.  The production of urea and glycogen were also increased, and glycogen storage was about five times greater in the hydrogen sulfide-treated group than in the control.  especially glycogen which was approximately five times greater compared to the control (p < 0.01). As a result of these experiments, the research group concluded that physiological concentrations of hydrogen sulfide increase the ability of human tooth pulp stem cells to undergo differentiation into liver cells.

Yaegaki commented, “Until now, nobody has produced the protocol to regenerate such a large number of hepatic (liver) cells for human transplantations.  Compared to the traditional method of using fetal bovine serum to produce the cells, our method is productive and, most importantly, safe.”  Yaegaki continued: “Moreover, these facts suggest that patients undergoing transplantation with the hepatic cells may have no possibility of developing teratomas or cancers, as can be the case when using bone marrow stem cells.”

Clearly, dental stem cells are from a tissue that is normally thrown out.  This new life for exfoliated teeth might provide a new role for these tooth-bound stem cells, and might also provide a new way to treat those with devastating liver diseases.  For example, systemic lupus erythematosis can decimate the patient’s liver, and without a transplant, the patient might die.  Adaptation of this protocol might drive other adult stem cell populations to produce liver cells for therapeutic purposes.  The potential is certainly great.