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Mechanical Stimulus Helps Stem Cells Grow, Study Finds

Mechanical stimuli-like shear or pressure-can change the way a stem cell develops, according to a study by researchers at Case Western Reserve University and Cleveland Clinic.

Mechanical Stimulus Helps Stem Cells Grow, Study Finds

Photo : Courtesy of Paul Tesar, PhD

"Stem cells change their activity when given subtle mechanical cues," says Melissa Knothe Tate, PhD, a professor of biomedical engineering and mechanical and aerospace engineering at Case Western Reserve, whose research is part of an emerging field, called stem-cell mechanics.

The discovery was made while studying a new procedure to heal major bone defects, which is a little unusual, Knothe Tate says. More often, basic research leads to practical applications in the field. In this case, however, the reverse happened and applied knowledge led to a better understanding of basic stem cell principles.

Ulf R. Knothe, MD, an orthopedic surgeon at Cleveland Clinic, developed this new procedure to address a major challenge in orthopedic surgery: repairing long-bone defects, or injuries in which at least an inch of bone is missing or has been damaged. The current standard of care in these defects is a limb-lengthening technique in which the surgeon places pins in the bone and attaches a "fixator" device located outside the skin. Using the fixator, the surgeon moves the bone about a millimeter a day to slowly pull the bone and create new bone in the defective area.

The technique has drawbacks.

"The pins used in this procedure provide a tract for bacteria to move from the skin into the bone," says Knothe. "As a result, it requires meticulous patient compliance and, typically, is painful as the bone segment is moved using the pins, which pulls through soft tissues, causing scarring."

To address these issues, Knothe developed a new procedure that utilizes the the bone's outer sheath, which is peeled back to reveal a healthy section of bone that is cut and moved in a single step to the defective area. The outer sheath is then surgically closed over the area where the bone was removed.

What Knothe found was surprising.

Existing bone stem cells from the outer sheath filled the entire zone where the bone had been removed with regenerative bone in two weeks. As the subject's weight shifted after surgery, the bones sent signals to the stem cells to regenerate, Knothe Tate explains.

"Weight-bearing activity actually helps create and strengthen bone," says Knothe Tate. "The cues stimulate the bone's stem cells into action, to replicate and grow. Similarly, if you stop bearing weight, for example, if you're bedridden after an injury, you can lose bone mass."

Knothe has performed the new bone surgery successfully in several patients, including a young woman with cerebral palsy, severe scoliosis and hip dysplasia, who was confined to a wheel chair. Exacerbating her scoliosis was the uneven length of her legs, so Knothe used the technique to lengthen the femur while replacing her hip joint with a prosthesis. The woman's scoliosis has improved and she is learning to walk again, Knothe says.

"We are learning to harness nature's innate healing potential," says Knothe. "As they say, 'Nature does it best.'"

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