How stimulating! A new way to repair broken bones

For those of us who live in earthquake country the recent devastating quakes in Nepal are a reminder, as if we needed one, of the danger and damage these temblors can cause. Many of those injured in the quake suffered severe bone injuries – broken legs, crushed limbs etc. Repairing those injuries is going to take time and expert medical care. But now a new discovery is opening up the possibility of repairing injuries like this, even regenerating the broken bones, in a more efficient and effective way.

shutterstock_18578173A study published in Scientific Reports  shows that it is possible to regrow bone tissue using protein signals from stem cells. Even more importantly is that this new bone tissue seems to be just as effective, in terms of the quantity and quality of the bone created, as the current methods.

In a news release senior author Todd McDevitt, Ph.D., said this shows we might not even need whole stem cells to regenerate damaged tissue:

“This proof-of-principle work establishes a novel bone formation therapy that exploits the regenerative potential of stem cells. With this technique we can produce new tissue that is completely stem cell-derived and that performs similarly with the gold standard in the field.”

McDevitt – who is now at the Gladstone Institutes thanks to a research leadership award from CIRM  – extracted the proteins that stem cells produce to help regenerate damaged tissues. They then isolated the particular factors they needed to help regenerate bones, in this case bone morphogenetic protein or BMP. That BMP was then transplanted into mice to stimulate bone growth. And it worked.

While this compares favorably to current methods of regenerating or repairing damaged bones it has a few advantages. Current methods rely on getting bones from cadavers and grinding them up to get the growth factors needed to stimulate bone growth. But bones from cadavers can often be in short supply and the quality is highly variable.

As McDevitt says:

“These limitations motivate the need for more consistent and reproducible source material for tissue regeneration. As a renewable resource that is both scalable and consistent in manufacturing, pluripotent stem cells are an ideal solution.”

He says the next step is to build on this research, and try to find ways to make this method even more efficient. If he succeeds he says it could open up new ways of treating devastating injuries such as those sustained by soldiers in battle, or by earthquake victims.

These Are the Cells You’re Looking for: Scientists Devise New Way to Extract Bone-Making Stem Cells from Fat

Buried within our fat tissue are stashes of stem cells—a hidden reservoir of cells that, if given the right cues, can transform into cells that make up bone, cartilage or fat. These cells therefore represent a much-needed store for regenerative therapies that rebuild bone or cartilage lost to disease or injury.

Finding cells that have bone-making potential is more efficiently done by looking at the genes they express (in this case, ALPL) than at proteins on their surface. The bone matrix being produced by cells is stained red in samples of cells that do not express ALPL (left), those that do express ALPL (right). [Credit: Darling lab/Brown University]

Finding cells that have bone-making potential is more efficiently done by looking at the genes they express (in this case, ALPL) than at proteins on their surface. The bone matrix being produced by cells is stained red in samples of cells that do not express ALPL (left), those that do express ALPL (right). The center image shows both types of cells prior to sorting [Credit: Darling lab/Brown University]

The only problem with these tucked-away cellular reservoirs, however, is identifying them and getting them out.

But now, researchers at Brown University have devised a unique method of identifying, extracting and then cultivating these bone-producing stem cells. Their results, published today in the journal Stem Cell Research & Therapy, seem to offer a much-needed alternative resource for growing bone.

Traditional methods attempting to locate and extract these stem cells focused on proteins that reside on the surface of the cells. Find the proteins, scientists reasoned, and you’ve found the cell.

Unfortunately, that method was not fool proof, and many argued that it wasn’t finding all the cells that reside in the fat tissue. So Brown scientists, led by Dr. Eric Darling found an alternative.

They knew that a gene called ALPL is an indicator of bone-making cells. If the gene is switched on, the cell has the potential to make bone. If it’s switched off, it does not. So Darling and his team devised a fluorescent marker, or tag, that stuck to the cells with activated ALPL. They then used a special machine to sort the cells: those that glowed went into one bucket, those that did not went into the other.

To prove that these ALPL-activated cells were indeed capable of becoming bone and cartilage, they then cultivated them for several weeks in a petri dish. Not only did they transform into the right cell types—they did so in greater numbers than cells extracted using traditional methods.

Hetal Marble, a graduate student in Darling’s lab and the paper’s first author, argues that tagging genes—rather than surface proteins—in order to distinguish and weed out cell types represents an important paradigm shift in the field. As he stated in a press release:

“Approaches like this allow us to isolate all the cells that are capable of doing what we want, whether they fit the archetype of what a stem cell is or is not. The paradigm shift is thinking about isolating populations that are able to achieve an end point rather than isolating populations that fit a strictly defined archetype.”

While their method is both precise and accurate, there is one drawback: it is slow.

Currently, it takes four days to tag, extract and cultivate the bone-making cells. In the future, the team hopes they can shorten this time frame so that they could perform the required steps within a single surgical session. As Darling stated:

“If you can take a patient into the OR, isolate a bunch of their cells, sort them and put them back in—that’s ideally where we’d like to go with this.”