New study may lead to speedy recovery from hip fractures

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 New study may lead to speedy
recovery from hip fractures

DURHAM: Each year in the United States more than 300,000 people are hospitalized for hip fractures. Almost half never recover well enough to live an independent lifestyle and, even worse, the one-year mortality rate is high, ranging from 12 percent to 37 percent.

A new discovery by doctors at the University of California Davis Medical Center (Sacramento) and Second Xiangya Hospital of the Central-South University (Hunan, China) might increase these patients’ chance for a speedy recovery. In a study published in STEM CELLS Translational Medicine, they demonstrate how mesenchymal stem cells (MSCs) engineered to over-express basic fibroblast growth factor (bFGF) accelerated the healing of fractures in mice.

"There are a handful of methods to chemically enhance the fracture healing process, but they have serious limitations," said study leader Wei Yao, M.D., associate director of the UC Davis Center for Musculoskeletal Health. "Side effects range from inflammation and abnormal bone formation to cancer. Thus, there is still an unmet medical need to treat fractures and shorten the time for bone healing."

bFGF is among a family of growth factors whose members are involved in everything from the formation of new blood vessels and wound healing to embryonic development and various endocrine signaling pathways. Previous studies demonstrate that bFGF injection leads to a profound regeneration of bone. However, prolonged exposure to bFGF ups the risk for cancer, inflammation and severe anemia."This led us to wonder if a combination of gene and cell therapies would work together to accelerate fracture repair and possibly be more effective than individual growth factors given systemically," said Dr. Yao.

To test their hypothesis, they collected MSCs from the adipose (fat) tissue of mice, then the MSCs were engineered to make more of the growth factor bFGF. They then generated a fracture in the right femur of each animal and injected the mouse’s genetic background-matched MSCbFGF back into it next to the site of the fracture. "Because MSCs given intravenously are likely to be trapped in the lung, we used intramuscular injection to bypass the risk of lung embolism," Dr. Yao said.

The mice were tested at days 7, 14, 21 and 35 post-fracture for various aspects of bone repair. Results indicated that the MSCbFGF led to an increased production of growth factors that, in turn, accelerated fracture repair by stimulating blood vessel growth and differentiation of both endogenous and exogenous MSCs into osteoblasts, which are the cells that form new bone.

"We concluded that transplantation of MSCs is more likely to enhance bone and cartilage regeneration when these cells were engineered to express growth factors  a finding that supports the use of MSCs as ‘factories’ to more safely produce a sustained release of low levels of bFGF over a controlled period for injury repair,” Dr. Yao said.

Our findings also indicate that the potential therapeutic window for effective MSCbFGF use is approximately one to two weeks," she added. "This novel treatment may reduce the time required for fracture healing."

“Due to the aging of the population, the worldwide incidence of hip fractures is expected to increase by at least 240 percent by 2050,” said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. “This research suggests a promising approach to improve treatment options and increase the likelihood of a successful recovery.”

Ref: “Acceleration of fracture healing by overexpression of bFGF in the mesenchymal stromal cells,” can be accessed at: http://www.stemcellstm.com

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