Speeding up bone growth by manipulating stem cells

June 25, 2012 By Steven Powell
Qian Wang at work among plants that host some of the building blocks of his nanomolecular scaffolds.

If you break a bone, you know you'll end up in a cast for weeks. But what if the time it took to heal a break could be cut in half? Or cut to just a tenth of the time it takes now? Qian Wang, a chemistry professor at the University of South Carolina, has made tantalizing progress toward that goal.

Wang, Andrew Lee and co-workers just reported in Molecular Pharmaceutics that surfaces coated with bionanoparticles could greatly accelerate the early phases of . Their coatings, based in part on genetically modified Tobacco , reduced the amount of time it took to convert stem cells into bone nodules – from two weeks to just two days.

The key to hastening bone healing or growth is to coax a perfectly natural process to pick up the pace.

"If you break a rib, or a finger, the healing is automatic," said Wang. "You need to get the bones aligned to be sure it works as well as possible, but then nature takes over."

Healing is indeed very natural. The human body continuously generates and circulates cells that are undifferentiated; that is, they can be converted into the components of a range of tissues, such as skin or muscle or bone, depending on what the body needs.

The conversion of these cells – called stem cells – is set into motion by external cues. In bone healing, the body senses the break at the cellular level and begins converting stem cells into new bone cells at the location of the break, bonding the fracture back into a single unit. The process is very slow, which is helpful in allowing a fracture to be properly set, but after that point the wait is at least an inconvenience, and in some cases highly detrimental.

"With a broken femur, a leg, you can be really incapacitated for a long time," said Wang. "In cases like that, they sometimes inject a protein-based drug, BMP-2, which is very effective in speeding up the healing process. Unfortunately, it's very expensive and can also have some side effects."

In a search for alternatives four years ago, Wang and colleagues uncovered some unexpected accelerants of bone growth: plant viruses. They originally meant for these viruses, which are harmless to humans, to work as controls. They coated glass surfaces with uniform coverings of the Turnip yellow mosaic virus and Tobacco mosaic virus, originally intending to use them as starting points for examining other potential variations.

But they were surprised to find that the coatings alone could reduce the amount of time to grow bone nodules from stem cells. Since then, Wang and co-workers have refined their approach to better define just what it is that accelerates bone growth.

Over the course of the past four years, they've demonstrated that it's a combination of the chemistry as well as the topography of the surface that determines how long it takes a stem cell to form bone nodules. The stem cells are nestled into a nanotopgraphy defined by the plant virus, and within that nanotopography the cells make contact with the variety of chemical groups on the viral surface.

Wang and his team are now asserting control over these variables. In the most recent effort spearheaded by Lee, they built up a layer-by-layer assembly underneath the virus coating to ensure stability. They also genetically modified the viral protein to enhance the interaction between the coating and the stem cells and help drive them toward bone growth.

Their efforts were rewarded with bone nodules that formed just two days after the addition of stem cells, compared to two weeks with a standard glass surface. They're also carefully following the cellular signs involved with success. BMP-2 is involved, but as an intrinsic cellular product rather than an added drug.

"BMP-2 is bone morphogenetic protein 2. It can be added as a protein-based drug, but it's a natural protein produced in the cell," said Wang. "We see upregulation of the BMP-2 within 8 hours with the new scaffold." They also find osteocalcin expression and calcium sequestration, two processes associated with bone formation, to be much more pronounced with their new coatings.

"What we've seen could prove very useful, particularly when it comes to external implants in bones," said Wang. "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 feel 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."

Chuanbin Mao, a professor in the department of chemistry and biochemistry at the University of Oklahoma who was not involved in the work, wrote in an e-mail that he was "amazed and excited" by the results. "The display of peptides on viruses, including Tobacco mosaic virus, is a powerful approach for studying how engineered virus particles can direct stem cell differentiation."

"The discovery that the display of a cell adhesion peptide on can enable the rapid differentiation of into bone-forming cells is very important for guiding scientists in designing a scaffold that can induce rapid bone formation in regenerative medicine."

Explore further: Stem cell treatment may offer option for broken bones that don't heal

More information: Mol. Pharmaceutics, Article ASAP DOI: 10.1021/mp300042t

Related Stories

Stem cell treatment may offer option for broken bones that don't heal

June 5, 2011
Researchers at the University of North Carolina at Chapel Hill School of Medicine have shown in an animal study that transplantation of adult stem cells enriched with a bone-regenerating hormone can help mend bone fractures ...

Smart materials that get bone to heal

November 4, 2011
Bone tissue is very good at self-healing, but in many situations the natural healing process is not sufficient. In a dissertation at Uppsala University, Sonya Piskounova shows how functional materials that she and her colleagues ...

A better way to grow bone: Fresh, purified fat stem cells grow bone faster and better

June 11, 2012
UCLA stem cell scientists purified a subset of stem cells found in fat tissue and made from them bone that was formed faster and was of higher quality than bone grown using traditional methods, a finding that may one day ...

Recommended for you

Drug found that induces apoptosis in myofibroblasts reducing fibrosis in scleroderma

December 15, 2017
(Medical Xpress)—An international team of researchers has found that the drug navitoclax can induce apoptosis (self-destruction) in myofibroblasts in mice, reducing the spread of fibrosis in scleroderma. In their paper ...

How defeating THOR could bring a hammer down on cancer

December 14, 2017
It turns out Thor, the Norse god of thunder and the Marvel superhero, has special powers when it comes to cancer too.

Researchers track muscle stem cell dynamics in response to injury and aging

December 14, 2017
A new study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) describes the biology behind why muscle stem cells respond differently to aging or injury. The findings, published in Cell Stem Cell, ...

'Human chronobiome' study informs timing of drug delivery, precision medicine approaches

December 13, 2017
Symptoms and efficacy of medications—and indeed, many aspects of the human body itself—vary by time of day. Physicians tell patients to take their statins at bedtime because the related liver enzymes are more active during ...

Study confirms link between the number of older brothers and increased odds of being homosexual

December 12, 2017
Groundbreaking research led by a team from Brock University has further confirmed that sexual orientation for men is likely determined in the womb.

Potassium is critical to circadian rhythms in human red blood cells

December 12, 2017
An innovative new study from the University of Surrey and Cambridge's MRC Laboratory of Molecular Biology, published in the prestigious journal Nature Communications, has uncovered the secrets of the circadian rhythms in ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.