Toxic Gas Prompts Mesenchymal Stem Cells to Become Bone Cells

Hydrogen sulfide smells like rotten eggs and is toxic to human life at moderate concentrations. Therefore, imagine the surprise of researchers when they discovered that low concentrations of this poisonous gas actually stimulate mesenchymal stem cells from bone marrow to differentiate into bone-making cells.

In a paper published in the journal Cell Stem Cell, Yi Liu from the Ostrow School of Dentistry at the University of Southern California and colleagues have discovered that hydrogen sulfide (H2S), acts as a “gaseous signaling molecule” that mesenchymal stem cells actually produce at sub-lethal concentrations.

H2S acts as a “gasotransmitter” that regulates multiple signaling pathways. To determine the extent of these pathways, Liu and his colleagues made mice that were unable to synthesize any H2S. The H2S-deficient mice showed distinct abnormalities in bone marrow mesenchymal stem cells. Namely, mesenchymal stem cells (MSCs) from H2S-deficient mice were unable to properly self=-renew or differentiate into bone-making cells (osteoblasts).

When Liu and others dug a little deeper, they found that H2S deficiency results in aberrant influx of intracellular Ca2+. Problems with calcium handling arose because calcium channels have amino acids that actually react with the H2S. This reaction between the calcium channels and H2S opens the channels and allows entry of calcium into the cell. Now cells contain a host of enzymes that need calcium to operate properly.  Without the reaction of the calcium channels with H2S, calcium does not influx into the cell and the differentiation of mesenchymal stem cells into bone-making cells stops.

schematic diagram R1.ppt

Why is this important? Consider some of the diseases of bone, such as osteoporosis, in which the bones thin and become fragile. Restoring mesenchymal stem cell function in osteoporotic patients with treatments of H2S levels at nontoxic levels may provide treatments for diseases such as osteoporosis that might arise from H2S deficiencies.

Thus by understanding stem cell biology better, we can potentially treat a disease like osteoporosis with small amounts of a stinky gas. Incredible, isn’t it?