Protein bath helps stimulate old marrow to form bone, study finds

July 18, 2013 by Krista Conger

Bone fractures in the elderly are notoriously slow and difficult to heal. Now, researchers at the Stanford University School of Medicine have identified a simple way to increase the effectiveness of a surgical process called bone grafting that may significantly speed the growth of new, healthy bone in response to trauma.

In studies involving mice and rabbits, the researchers found that a quick dip in a bath of a signaling protein called Wnt3a can rev up sluggish bone-forming cells in older animals that would normally be unable to heal a fracture. If the simple treatment is eventually found to be effective in humans, it may significantly improve the success of , which are performed more than 500,000 times every year in the United States.

"We're very focused on designing a treatment that could be easily employed by in the normal course of bone grafting," said professor of surgery Jill Helms, DDS, PhD. "We've shown that when we temporarily treat bone marrow from aged animals with Wnt before transplanting the cells into a fracture site, we see really robust ."

Helms is the senior author of the study, published July 17 in the Journal of Bone and Joint Surgery. Philipp Leucht, MD, a resident in orthopaedic surgery at Stanford, is the lead author.

"Hip fractures in elderly people nearly triple the risk of dying within a year of the injury, and a rapidly aging population demands more effective treatments for this type of trauma," said Helms.

The temporary nature of the treatment described in the paper, and the fact that it is conducted outside the body, is important because Wnt is a potent stimulator of growth and development for many types of cells. Injecting the protein into the body, where it can affect cells willy-nilly, raises the specter of uncontrolled proliferation and cancer.

Bone grafting involves transplanting whole marrow—which is rich in that form bone, blood and the cells of the immune system—into a fracture site. Although the use of a patient's own tissue is preferable to avoid rejection, marrow from older people looks and acts nothing like young marrow; as we age, our bone marrow begins to look more like a fatty tissue than the industrious blood- and bone-producing factory of children or younger adults.

As a result, orthopaedic surgeons sometimes use donor bone or marrow, or rely on the activity of drugs that incorporate bone morphogenetic proteins, or BMPs, to stimulate bone growth. But the hunt's been on to find alternatives that allow the use of a patient's own cells without medications.

The new finding is an extension of previous work in Helms' lab aimed at devising a way to produce a biologically active form of the finicky Wnt molecule, which is difficult to purify and dissolve in liquids. In 2010, Helms and Roeland Nusse, PhD, a Stanford professor of developmental biology, showed that they could attach the Wnt protein to tiny, water-friendly molecular bubbles called liposomes that could be injected directly into lab animals with fractures. The previous study found that this treatment promoted the rapid growth of new bone, but safety concerns about its use in humans remained.

In the current study, Helms and Leucht harvested whole from laboratory mice genetically engineered to express a fluorescent protein. They then transplanted this marrow into 2-millimeter round holes they'd created in the skulls of anesthetized mice and followed the fate of the fluorescently labeled, transplanted cells.

The researchers found that within seven days, the transplanted marrow cells had remained in the injury site and begun to divide robustly. Over time, the defects in the mice that had received the bone graft healed completely. In contrast, the untreated mice were unable to fill the hole with new bone.

When Leucht and Helms repeated the experiment with marrow from older animals—laboratory mice over 40 weeks old—they saw a very different result. Recipient animals now generated much less bone at the injury site. And a closer look showed that the older marrow expressed lower levels of Wnt protein compared with that of the younger animals.

Finally, the researchers exposed the aged donor marrow to a brief bath of either Wnt3a or a control solution before transplanting them into the recipients. Within seven days, animals that received the Wnt-treated marrow had twice as much new at the injury site as control animals.

The researchers repeated their experiments on rabbits, which have longer bones that more closely resemble those of humans. Again, they found that treating old marrow briefly with Wnt3a significantly improved the cells' ability to heal a simulated fracture in the leg of recipient animals.

"Our findings have direct implications for humans," Helms said. "As we age, our healing is much less robust. We now have reason to believe that this might be due in part to a general decline in Wnt signaling. If we can temporarily activate this signal while the marrow is outside the body, we might be able to provide a transient, much-needed boost to the activity of stem cells in the marrow."

Explore further: New findings may help overcome hurdle to successful bone marrow transplantation

Related Stories

New findings may help overcome hurdle to successful bone marrow transplantation

May 28, 2013
Blood diseases such as leukemia, multiple myeloma, and myelodysplasia can develop from abnormal bone marrow cells and a dysfunctional bone marrow microenvironment that surrounds these cells. Until now, researchers have been ...

Fat in organs and blood may increase risk of osteoporosis

July 16, 2013
Excess fat around the belly has recently been identified as a risk factor for bone loss. Now, a new study has determined that excess liver and muscle fat also may be detrimental to bone.

Type 2 diabetes patients transplanted with own bone marrow stem cells reduces insulin use

June 28, 2013
A study carried out in India examining the safety and efficacy of self-donated (autologous), transplanted bone marrow stem cells in patients with type 2 diabetes (TD2M), has found that patients receiving the transplants, ...

Epidermal growth factor aids stem cell regeneration after radiation damage

February 3, 2013
Epidermal growth factor has been found to speed the recovery of blood-making stem cells after exposure to radiation, according to Duke Medicine researchers. The finding could open new options for treating cancer patients ...

Discovery may help prevent chemotherapy-induced anemia

May 5, 2013
Cancer chemotherapy can cause peripheral neuropathy—nerve damage often resulting in pain and muscle weakness in the arms and legs. Now, researchers at Albert Einstein College of Medicine of Yeshiva University have discovered ...

Recommended for you

World's first child hand transplant a 'success'

July 19, 2017
The first child in the world to undergo a double hand transplant is now able to write, feed and dress himself, doctors said Tuesday, declaring the ground-breaking operation a success after 18 months.

Knee surgery—have we been doing it wrong?

July 18, 2017
A team of University at Buffalo medical doctors have published a study that challenges a surgical practice used for decades during arthroscopic knee surgery.

New tools help surgeons find liver tumors, not nick blood vessels

July 17, 2017
The liver is a particularly squishy, slippery organ, prone to shifting both deadly tumors and life-preserving blood vessels by inches between the time they're discovered on a CT scan and when the patient is lying on an operating ...

Researchers discover indicator of lung transplant rejection

July 13, 2017
Research by scientists at Dignity Health St. Joseph's Hospital and Medical Center's Norton Thoracic Institute was published in the July 12, 2017 issue of Science Translational Medicine titled "Zbtb7a induction in alveolar ...

New device could make closing surgical incisions a cinch

July 7, 2017
Like many surgeons, Dr. Jason Spector is often faced with the challenge of securely closing the abdominal wall without injuring the intestines. If the process goes awry, there can be serious consequences for patients, including ...

Success with first 20 patients undergoing minimally invasive pancreatic transplant surgery

June 29, 2017
Surgeons at Johns Hopkins Medicine report that their first series of a minimally invasive procedure to treat chronic pancreas disease, known as severe pancreatitis, resulted in shorter hospital stays, less need for opioids ...


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.