Published originally in the winter 2010 issue of Berea College Magazine
by Julie Sowell
A few years ago, Dr. Rocky Tuan, ’72, an expert in musculoskeletal systems and a pioneer in the field of tissue engineering and regenerative medicine, was asked by doctors at Walter Reed Army Medical Center to help them study a problem affecting soldiers returning from combat in Iraq and Afghanistan. Wounds to their arms and legs weren’t healing properly. “People who have blast injuries have a very high incidence of heterotopic ossification,” says Rocky. ”Bone forms where it’s not supposed to form, particularly after amputation, and we wanted to know why.” The condition causes deformity and pain at the amputation site and makes wearing a prosthesis difficult.
There is presently no good way to prevent or treat the problem, but Rocky has been working on a way to use the soldiers’ own stem cells for a cure. Studying samples of the soldiers’ injured muscle in his lab, he and his team found stem cells present in unusually large numbers.
“These stem cells have all kinds of potentially regenerative activities,” Rocky says. “I think it’s possible these stem cells can be used to repair nerves and suppress the bone formation.” The project is just one of several going on in Rocky Tuan’s lab at the University of Pittsburgh School Of Medicine’s new Center for Cellular and Molecular Engineering, where he is the founding director, as well as professor and executive vice chairman of the Department of Orthopaedic Surgery. A pioneer in the tissue engineering and regenerative medicine field, Rocky leads an interdisciplinary team there whose members are creating cell-based therapies for musculoskeletal diseases and injuries that can be turned into a variety of products for healing and cures.
Rocky has studied the musculoskeletal system and its workings for more than 30 years. His interest began in graduate school with a literal chicken and egg question that resulted in an important scientific discovery.
After graduating from Berea College with a degree in chemistry, Rocky enrolled at Rockefeller University in New York, where he earned his doctorate in 1977. “One of the things about the Rockefeller is they encouraged students to search on their own for what really, truly interested them,” he says. With his advisor’s blessing, he spent a month at the library studying possible research topics, finally deciding on the development of the chick embryo. “A chicken develops independently, outside the mother, literally. It has the power to do everything on its own. I thought that was a very fascinating model.” And there was a mystery about the chick’s development worth investigating. “The chicken starts out as a little dot on top of the yolk and then at the end it comes out and it’s walking around. It has lots of bones. Where did they come from?” Rocky’s discovery of the transport mechanism of calcium from the chicken eggshell was the substance of his doctoral dissertation and launched his professional career.
How the young man from Hong Kong got his start at Berea College was about as improbable as a full-blown chick emerging from an egg. “I guess it was fate,” Rocky says. In high school he happened to attend a presentation in Hong Kong with then-Berea-President Francis Hutchins on the program. “I talked with him afterward and he described his school to me,” Rocky says. “I thought it was an interesting concept.” A thorough researcher even then, he read all he could about Berea College and Hutchins before deciding to apply. “It was a great opportunity,” he says. “It would have been impossible for my family to pay tuition for college then.” His brother James, who now works in the nutritional biotechnology field, also attended Berea, graduating in 1978.
Several Berea College professors stand out as important to him—chemistry professors Gus Levey and Tom Beebe, physics professor Tom Strickler, and Rolf Hovey in music. “My education at Berea was tremendous,” Rocky says, who adds that he would not have received the same broad exposure to the liberal arts under the British system in Hong Kong. In addition to taking all the science courses he could, he also had the chance to pursue his lifelong love of music. Once Rocky decided to pursue chemistry as a career, Beebe encouraged him to get some research experience. “He gave me a big pile of stuff to read over,” Rocky says. “There were opportunities for research in the region, but also throughout the country.” He got into a summer research program in a bio-chemistry lab at the University of Louisville Medical School, under the tutelage of the late Dr. Calvin Lang, and returned the following summer. “That was what really got me started wanting to do research.”
After that came postdoctoral fellowships at Harvard Medical School, including the Department of Orthopaedic Surgery at Children’s Hospital and the Department of Medicine at the Massachusetts General Hospital. Following his fellowship training, Rocky was appointed in 1980 as assistant professor and then later associate professor in the Department of Biology at the University of Pennsylvania in Philadelphia, where he continued to explore the biology of musculoskeletal structure and development. After his recruitment in 1988 to direct orthopaedic research and appointment as Professor in the Department of Orthopaedic Surgery at Thomas Jefferson University, also in Philadelphia, his research interests began to take on a new direction, he says. “I started thinking, ‘Well, it’s okay to study how everything’s put together, but in the end, things fall apart. How can we mend all these structures?’”
Not treat, but mend. Regenerative medicine was still in its early stages when, in 1997, Rocky established the nation’s first Cell and Tissue Engineering doctorate program at Jefferson, a transdisciplinary program that would train a new generation of “cross-cultural biomedical scientists committed to regenerative medicine and the development of functional tissue substitutes.”
Rocky has remained on the leading edge of regenerative medicine research and education. In 2001, he was recruited to join the elite corps of scientists at the National Institutes of Health (NIH) as chief of the newly created Cartilage Biology and Orthopedics Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, leaving in 2009 for his present position at Pitt.
His wife of 33 years, Dr. Cecilia Lo, is also a research scientist, specializing in congenital heart disease. She was chief of the laboratory of develop-mental biology at the National Heart, Lung, and Blood Institute of the NIH, and currently is the founding chair of the University of Pittsburgh School of Medicine’s newly established department of developmental biology.
While problems with the musculoskeletal system are among the most common reasons people see a doctor, the true importance of the scientific research goes deeper than that for Rocky. “We are how we look, mostly, because of skin and bones,” he says. “The bones give us structure, and then we cover everything with skin, with a little bit of muscle in the middle.
What this means is that if you have any defects in your skeletal structure or you’re missing a limb, it’s immediately apparent, but also in many cases disabling or confining. Short of dying, the loss of physical freedom is just about the worst thing that can happen to a human being. Orthopaedic science and medicine is about restoring freedom and mobility to people,” says Rocky. “That’s why what we do is really, really important.”
So he turned his attention to the enormous potential of tissue-engineering technologies. Osteoarthritis provided a clear example of how this totally new approach to treatment could change outcomes. Affecting 27 million Americans over the age of 25, osteoarthritis is caused mostly from normal wear and tear, but genetics and lifestyle also play a role. It often starts with a tear in joint cartilage. As the tear worsens, the cartilage deteriorates, causing pain. The surrounding joint tissue becomes irritated and the body reacts by forming more tissue, known as bone spurs, causing more pain and reducing movement.
“A major advancement in orthopedics was—and it still is— restorative surgery,” says Rocky. “If your joint is falling apart, we take everything off. A device made of plastic and metal is put in, and the joint functions again.”
At least for a while. The best case scenario for artificial joints is that they can last on the average a maximum of about 10-15 years. However, the surgery can only be performed one more time, at the most twice, and each time with diminishing benefits. “Total joint replacement is a terrific procedure that has restored mobility, self-esteem, and happiness to many, many people,” says Rocky. “A million procedures are done every year world-wide in hip and knee replacements.”
Rocky’s approach is biological. “Wouldn’t it be nice if you could make something exactly like your natural joint to restore you back to your old self?” he asks. His idea is to engineer tissue instead of engineering a device. A patient’s own bone marrow stem cells are reprogrammed to grow into large pieces of cartilage, which is then transplanted back into the patient. “It’s like a skin graft,” says Rocky, “and when it becomes available, you’ll only need it done once.”
There are other fascinating projects going on in Rocky Tuan’s labs, too. “We’re trying to repair the meniscus, the semicircular wedge that’s the washer in your knee, and we’re engineering substitutes for the intervertebral discs, the shock absorbers in the spine between the vertebrae,” he says. There is a huge need for the treatment. “Right now, the disc is removed entirely and the vertebrae fused together. This stops the pain but reduces the patient’s mobility and can lead to other problems.”
The basic building blocks for all of these engineered products are adult stem cells. Unlike embryonic stem cells, which have ethical and moral issues related to their use, adult stem cells are found in the body, primarily in bone marrow. The adult stem cells that Rocky works with, called mesenchymal stem cells (MSCs), can become all of the cell types that make up musculoskeletal tissue—bone, cartilage, muscle, tendons, ligaments, and even nerves and blood vessels. In order to turn cell behavior into cures, however, it first requires a thorough study of the biology of these MSCs because “ultimately the cell is the tissue engineer,” Rocky says. “We’re just the cheerleaders.” Innovative new approaches and laboratory devices have had to be invented or adapted for this type of research, that include nanotechnology, biomaterials construction, and bioreactors, for which Rocky holds two associated patents.
Doctors have been using adult stem cells to treat autoimmune diseases and some types of cancer for a number of years. Adult equine stem cells are also being successfully used to heal torn ligaments and regenerate tissue in horses. Rocky says it will be several years before most of the therapies he and his team are developing will be available. “There are a variety of complicated problems we have to find solutions for before these kinds of therapies can be used in humans,” he says. “We need more studies to be sure that these therapies are safe and nontoxic, as well as effective. We have to worry about any immune reactions from the host, because we’re replacing, not repairing.” Still, various forms of regenerative medicine are projected to revolutionize healthcare within the next 10-20 years.
Thanks to leaders of this revolution like Dr. Rocky Tuan, those of us with knee and back injuries, traumatized limbs, and worn out joints, will be standing restored and stronger one day soon.