Achieving a spinal fusion or regenerating a diseased spinal disk with a simple injection may sound to some like science fiction, but Francis H. Shen, MD, is working to make such surgery-free treatments possible—with the help of a Clinician Scientist Award from the Orthopaedic Research and Education Foundation (OREF).

Dr. Shen, an assistant professor in the department of orthopaedic surgery at the University of Virginia School of Medicine, had previously received an OREF-Zimmer Career Development Award; the Clinician Scientist Award, presented to him in 2007, provides an annual stipend of $100,000 for three years to compensate for the loss of income associated with devoting more time to research and less time to clinical practice. He will use the funding to continue his search for new sources of bone tissue and, ultimately, less invasive treatments for spinal disorders.

“I’m just beginning to understand what an honor it is to receive this award,” said Dr. Shen. “And I’m beginning to understand the significance it has for me as a clinician scientist, for my career, for what our lab can do, and for how much we can accomplish for our patients.”

“This award recognizes Dr. Shen’s tremendous work in research and his great potential for the future,” said Cato T. Laurencin, MD, PhD, chair of the department of orthopaedic surgery and Lillian T. Pratt distinguished professor. “It affirms to my faculty what they already know: that scientific inquiry is the key to the future of orthopaedic surgery as a profession, and that dedicated, protected time is key to developing clinician scientists.”

The challenge of fusion
“One of the biggest challenges we have as spine surgeons is achieving fusion,” Dr. Shen explained. “I am looking for ways of encouraging bones to knit together across vertebrae. Fusion is the ultimate goal for a variety of clinical spine problems—ranging from trauma that results in a fracture or instability to spinal stenosis, which can result in instability and a need to stabilize the spine, to infection or tumors that require removal and replacement of portions of the spine.”

Although autologous bone does the best job of encouraging bone growth, it is limited in supply, extremely painful to extract, and is not always an option in cases of infection or tumor. Cadaver bone brings increased risk of infection, even if the tissue has been irradiated, and raises religious and other concerns for some patients. In addition, both procedures pose routine surgical risks.

“My research is looking for an alternative to autologous or cadaver bone,” said Dr. Shen. “Perhaps by using pluripotential stromal cells from your own body—cells found in connective tissue with the ability to develop along different lineages—we can, for example, convince a fat-derived stromal cell to become a bone cell and then augment the process by using growth factors and by creating the right environment.”

Specifically, Dr. Shen is interested in understanding how certain growth factors encourage former fat cells to become bone cells and how they induce biomechanical differentiation—taking on the form and function of a joint, tendon, or bone.

“During the past 3 to 4 years, we’ve demonstrated success in vitro and in vivo in animals. I’ve been able to take certain cells, transfect them, and actually grow bone cells, then have scaffold polymers resorb and leave a structure in their place that looks like—and is biomechanically similar to—bone,” explained Dr. Shen. “We’re doing this now in animals so, hopefully in the next 3 to 5 years, we may be able to be in clinical trials in humans. The possibility of delivering a protein by percutaneous injection to a patient in need of fusion or disk regeneration, with fewer side effects than surgery and far greater gains achieved, may not be very far off.”

New treatment opportunities
Dr. Shen also sees an opportunity to uncover new treatments for diseases that target bone tissue by learning more about how bone breaks down. Recently, he has been considering the process of bone resorption, which occurs in diseases such as osteoporosis, osteopenia, and osteolysis, as well as in cancer and tumor cells.

“If we could learn how bone breaks down and why, and identify ways to halt the breakdown,” he said, “and if we combine that with what we are learning about the ability of certain cells under certain conditions to make bone, we may make additional gains from looking at both ends of the bone process.”

Dr. Shen is currently examining breast cancer cells, which are known for being aggressive in breaking down bone. Working with endocrinologists and using human breast cancer cells in animals, Dr. Shen will develop a spinal metastases model. Eventually, he hopes to find ways to retard or even reverse the breakdown of bone tissue in breast cancer patients.

For Dr. Shen, research practice and clinical practice are one and the same.

“In our lab, everything we do contributes to improving the quality of life for our patients—and for ourselves, because we will all be patients one day, as will our children and our grandchildren. That’s why the research that OREF funds is so important. Our profession—and our quality of life—depend on research.”

OREF Clinician Scientist Award celebrates 5th anniversary
The OREF Clinician Scientist Award was established by Dr. Zachary B. and Mrs. Kathleen Friedenberg in 2003 to encourage young orthopaedic surgeons to pursue careers as clinician scientists, with a special emphasis on continued research. To date, five gifted investigators have been able to pursue highly promising studies with generous support from the Friedenbergs, Dr. Dane and Mrs. Mary Louise Miller, and The Journal of Bone and Joint Surgery. Award recipients include the following:

2003—James Robert Slauterbeck, MD
2004—David Louis Glaser, MD
2004—Javad Parvizi, MD
2007—Cristin M. Ferguson, MD
2007—Francis H. Shen, MD

To apply for a 2008 Clinician Scientist Award, visit www.oref.org/grants today; applications are due October 1, 2007.

To discuss a gift to fund a Clinician Scientist Award, contact Ed Hoover, associate vice president, development, at (847) 384-4354 or hoover@oref.org.