Sometimes great scientific discoveries are the result of serendipity, The German organic chemist August Kekulé supposedly came upon the structure of the chemical benzene because of a day-dream in which he saw a snake biting its own tail. This story illustrates that even brilliant scientists conceive of some of their greatest ideas in ways that are accidental.
Today’s discovery is a stem cell version of August Kekulé’s day-dream. Researchers at the University of South Carolina have been interested in growing bone from stem cells. In order to get the cells to form bone, Qian Wang, Robert L. Sumwalt Professor of Chemistry at the University of South Carolina, grew mesenchymal stem cells (MSCs) from bone marrow on plastic culture dishes. However, he wanted to test the ability of different surfaces to influence bone formation by MSCs. In order to compare each surface he tested with something that seemed rather innocuous, Wang decided to use plant viruses.
Plant viruses such as turnip yellow mosaic virus are completely harmless to animal cells and they can be isolated in gram quantities from cabbages, which makes them very inexpensive to work with. Wang decided to coat his culture dishes with these plant viruses in order to have something that was a sort of ground-zero surface that did not do anything to the cells. Except there was one problem: The plant virus-coated surfaces helped the stem cells make bone faster than anything else Wang’s group examined.
This gave Wang an idea. When bones break in our bodies, stem cells make new bone at the site of the break in order to help the bones reform and heal themselves. The process can take some time and people with broken bones are usually incapacitated for some time. Wang wondered, “what if we could make that healing process go faster?”
Wang explains: “With a broken femur, a leg, you can be really incapacitated for a long time. In cases like that, they sometimes inject a protein-based drug, BMP-2 [bone morphogen protein-2], which is very effective is speeding up the healing process. Unfortunately,, it’s very expensive and can also have some side effects.” One of those side effects is an increased risk of tumors.
By coating glass slides with turnip yellow mosaic viruses (TYMVs) or tobacco mosaic viruses (TMVs), Wang and his colleagues found that the stem cells did not take nearly as long to form bone in culture.
Since making that discovery four years ago, Wang has been trying to determine what is it about the viruses that cause the MSCs to make bone so effectively. It turns out that the viruses form a specific topography on the glass slides and this topography forms a kind of “easy chair” for the MSCs. The next question was, “Could this easy chair be made into more of a Sleep Comfort Bed for the MSCs?” Could they improve it?
Wang and his group set about chemically modifying the surfaces of the viruses and binding things to them in order to stabilize the interaction of the viruses with the MSCs and the slide.
The results were astounding. With the right concoction of plant viruses coating the glass slides, the right molecules bound to the plant viruses, and the right culture medium recipe, Wang’s group found that they could induce MSCs to form bone in two days. The cells are also make many proteins that are specific to bone formation.
According to Wang: “What we’ve seen could prove very useful, particularly when it comes to external implants in bones. With those, you have to add a foreign material, and knowing that a coating might increase the bone growth process is clearly beneficial. But more importantly, we fell we’re making progress in a more general sense in bone engineering. We’re really showing the direct correlation between nanotopography and cellular response. If our results can be further developed, in the future you could use titanium to replace the bone and you might be able to use different kinds of nanoscale patterning on the titanium surface to create all kinds of different cellular responses.”
In many ways this work is just the beginning of what will almost certainly become a remarkable advance in bone engineering.