Hopkins turns muscle into bone New team working to help body make bone replacements.

January 23, 1992|By Frank D. Roylance

Johns Hopkins Hospital is assembling a team of scientists that will work to perfect a kind of biological alchemy that has already succeeded in turning muscle into bone.

Experiments with manipulation of the body's own repair mechanisms suggest human beings soon may be able to generate their own skeletal replacement parts inside their own bodies.

Hip joints worn down by age or disease, facial bones damaged by accident or congenital deformity, and slow-healing fractures might all be repaired or replaced with the patient's own bone tissue, manufactured to precise specifications inside his own body.

"We see this as the wave of the future," says Dr. Richard N. Stauffer, the newly appointed director of Hopkins' orthopedics department. "We have definitely entered a new era in medicine and research, and without question we have entered a new era of orthopedic medicine."

In time, he says, today's sophisticated artificial implants, pins, braces and other mechanical prosthetic devices will begin to seem clumsy and primitive.

The first experiments using human subjects may begin at Hopkins in the next several months, Dr. Stauffer says, although he declines to describe the project. It may be five years before the technology is generally available.

With 10 scientists, Hopkins' new Laboratory for Musculoskeletal Research, which opened officially this month, is to be led by Dr. A. Hari Reddi, a Hopkins cell biologist formerly with the National Institutes of Health in Bethesda.

In experiments on rats, Dr. Reddi and colleagues at NIH and Washington University School of Medicine in St. Louis already have transformed flaps of thigh muscle into bones molded in the shape of the rat's femoral head -- the upper thigh bone and hip joint.

That bone is the rat counterpart of the hip joint so often replaced with artificial devices in elderly Americans.

The research shows that the bone muscle transformed itself into bone because it was stimulated by injection with osteogenin, a recently purified natural protein that the body produces to stimulate bone growth. The shaping was achieved by clamping the muscle -- which remained attached to its blood supply -- into a rubber mold in the form of the femoral head.

The whole assembly was then implanted inside the rat's abdominal walls for 10 days.

The new bone appears to have a normal internal structure, Dr. Reddi says. Additional tests will determine whether the generated bone is as strong as the original.

Scientists have long known that bone has remarkable powers of regeneration. Through a "cascading" sequence of biological responses, Dr. Reddi says, the bone first creates a cellular "callus" at the injury site, then transforms it into cartilage and, finally, regenerated bone tissue.

In this way, a broken bone is capable of spontaneously regenerating itself, filling in gaps and knitting itself back together.

"There has been a continuing quest to find what is the principle of this," Dr. Reddi says.

Meanwhile, surgeons are often faced with bone injuries or defects that go beyond the body's own reconstructive powers, according to Dr. Reddi's report of his work last fall in the Journal of the American Medical Association.

In those cases, bone grafts and transplants have offered some help. But the availability of such tissue is limited. The operations don't always work, and the grafts can't always be formed into the necessary shapes.

The capacity of certain bone proteins to induce bone growth in other tissues has also been known since the 1940s. Early experiments used bone extracts to produce bone growth in rabbit muscle.

Dr. Reddi and his colleagues have spent the last 20 years searching for and purifying that powerful bone growth protein, called osteogenin, and identifying its genetic codes.

They found that it exists in minute amounts in the body, constituting barely a billionth of the bone's mass by weight. But they have now cloned the protein, and bioengineering laboratories are producing it in useful quantities in a half-dozen forms through recombinant DNA technology.

The potential for healing is enormous, Dr. Stauffer says.

In addition to stimulating the development of molded bone segments from muscle tissue, osteogenin preparations may eventually be used to provide a more natural "anchor" for artificial implants, raising the success rate of implant surgery, he says.

They also could play a role in dental surgery, especially where periodontal disease has eroded bone structure in the jaws.

Future research may even discover similar proteins that stimulate the regeneration of cartilage and muscle tissue, opening the possibility that humans, like some more primitive life forms, may one day be able to regenerate lost or damaged parts.

Such things, says Dr. Stauffer, "are beginning to sound less and less like science fiction."

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