Shark bites, mine explosions, car crashes may not mean loss of limb, says scientist
March 22, 2010
Hope and pray you or someone you know never benefits from Roger Farrar's pioneering research.
To appreciate the value of his work, you'd have to have most of your calf bitten off by a shark, an arm maimed when your car's broadsided by a bus or your leg almost removed by a mine explosion in Afghanistan.
Farrar, an exercise physiologist in The University of Texas at Austin's College of Education, has conducted studies on how to regenerate muscle that's been lost due to a serious injury or accident. In response to moderate damage skeletal muscle normally repairs and remodels itself, but if there's significant muscle, blood vessel and connective tissue loss, like one might suffer from a gunshot wound, the body's natural repair capabilities just aren't sufficient to tackle the job.
Farrar's research is distinctive because it shows promise in rebuilding load-bearing, or skeletal, muscle in arms and legs rather than cardiac or vascular muscle. This repair of the hard-working skeletal muscles is a feat that's never before been accomplished.
Even more impressive than the ability to "grow" more muscle is that after the damaged muscle has regenerated, Farrar's experiments indicate it can regain almost 100 percent of its pre-injury strength and functioning. If lab results translate well to "real life," patients who undergo this surgery will be able to run, walk, lift, jump and throw after healing from the procedure.
To study muscle regeneration, Farrar removed a third of the calf muscle from the lateral side of a rat's leg, taking the full depth and thickness of the muscle. The removed oval-shaped chunk of muscle simulated what might be lost in a severe injury.
After removing a portion of muscle, he then sutured a piece of honeycombed connective tissue, called the extra-cellular matrix, in the wound defect area. The extra-cellular matrix is a web-like, whitish tissue that can be seen in cuts of meat, like steak, and that acts as a kind of scaffold on which muscle cells can hang. It's a defining feature of connective tissue in animals and, in Farrar's procedure, served as a fertile field for new muscle growth.
After Farrar attached the extra-cellular matrix, he injected around one to two million adult stem cells into it.
"We're able to use stem cells from the bone marrow or adipose tissue of the adult animal," says Farrar, who's a professor in the Department of Kinesiology and Health Education. "Stem cells harvested in this way have been shown to be 'immune-privileged.' This means the immune system doesn't have a problem accepting them. In my experiments, these cells are isolated, grown in culture and infused into the damaged area.
"What's especially promising is that techniques are being explored to use stem cells isolated from adipose tissue when a patient is first brought into a surgical suite. These are called 'point of patient care' stem cells and in Japan and Europe they're already administering point of patient care to humans. There's a patent pending here in the U.S. for use in humans, specifically for breast reconstruction following surgery for cancer, as well as for other non-load bearing muscles. "
After the stem cell infusion, which stimulated hormone release and cell growth, Farrar followed the regeneration of the muscle. He tested how well the growing muscle contracted and functioned, and determined that the growing and regenerating cells were in fact muscular tissue. One challenge in muscle regeneration is to minimize the scar tissue.
After six weeks, Farrar found that the muscle mass and volume were back to 90 percent and the maximal force that the muscle was able to generate was up to 95 percent.
"These data are encouraging because not only is the function restored," says Farrar, "but also cosmetically the muscle looks the same as the control leg on the contra-lateral side. A human who had this procedure done would not have an ugly visual reminder of the injury or feel that that area was conspicuous to others."
So far, he has only assessed regenerated muscle after six weeks of recovery.
"Two critical questions remain that I hope my future studies will answer," says Farrar. "I need to find out whether or not the newly grown tissue will remain healthy and functional for a long period of time and for this to occur there will need to be a complete restoration of nerve and blood supply to the tissue."
Farrar also has completed a second, related study that has enormous implications for the military and injuries sustained in combat. This research addresses the muscle damage that happens when a tourniquet is applied to restrict blood flow during some surgeries.
"If your ankle is badly injured," says Farrar, "a surgeon will have to operate, and to do that she will need a bloodless field around the ankle. To cut off blood from the lower leg, a pneumatic cuff is applied, the operation occurs, and when the cuff is removed, there's significant muscle damage to the area that was denied blood flow.
"A tourniquet is kept on for two hours max during a medical procedure, and even after just two hours the reintroduction of blood causes muscular damage. The muscle is so severely damaged that seven days later it can only generate about 25 to 30 percent of its original power. This damage to muscular tissue is worse in older individuals, and the restoration of muscular function is slower."
Farrar is examining a variety of treatments to reduce damage and enhance regeneration following tourniquet applications, including stem cell infusion. Recent literature on the subject indicates that the infusion of stem cells into brain or heart tissue, following damage to those areas, enhances restoration of function in that tissue.
Success in this area of research would have extensive applications internationally — the latest data indicate about 20,000 tourniquets a day are applied during medical procedures worldwide.
"Use of adult stem cells from bone marrow or adipose tissue to treat tissue injury and disease, period, is multifaceted, with far reaching implications," says Farrar.
According to Farrar, approximately 70 percent of wartime wounds sustained by U.S. military personnel in combat are to the soft tissue of the legs and arms, and operations performed on the extremities after battlefield injuries make up the highest percentage of surgical procedures. Even when a limb can be saved, he says, the initial damage and loss of muscle and surrounding tissue leave the soldier with a permanent physical handicap.
Farrar's stem cell and muscle regeneration research was funded by a three-year, $550,000 grant from the U.S. Army, and wounded soldiers will be the largest population to benefit from his discoveries.
"Improvised explosive devices and land mines are the most common causes of serious muscle tissue damage to deployed soldiers," says Col. Barbara Springer, director of the Proponency Office for Rehabilitation and Reintegration in the U.S. Army Office of the Surgeon General, and a College of Education alumnus. "The first priority is to salvage a wounded limb, if possible, but if it cannot be salvaged, it's amputated. Obviously any procedure that allows a person to keep his or her arms and legs is going to mean a much better quality of life for that person. The prosthetics that are available now are wonderful, but nothing precisely approximates the natural and normal functioning of a person's own arms and legs.
"There also are significant mental, emotional and body image issues surrounding amputation. I've met wounded soldiers who have elected to use a cosmetic arm prosthesis that was more 'real' looking than one that would be more functional. Right now, rehabilitation from serious muscle tissue injury to limbs can take anywhere from two or three months to a year or two. Depending on what other injuries a soldier has suffered and the extent of damage to the muscle, recovery time after muscle regeneration surgery could be as little as six weeks, perhaps."
Farrar has had the pleasure of visiting Walter Reed Army Medical Center, where Springer was Chief of Physical Therapy Services before moving to the Office of the Surgeon General, and seeing the fierce determination that many of the wounded bring to the healing process.
"It's one of the most emotional environments anyone can experience," says Farrar. "These soldiers have lost limbs, suffered burns, internal injuries, and more, and they show such optimism regarding recovery. They're asking how soon they can rejoin their units overseas and be of use again.
"Recovery for many of them is miraculously rapid, just purely as a result of their extremely hard work, and a few even go on to participate in competitions like the Paralympic Games. I think that's just incredible. If there's anything I can do, through my research, to help them and anyone else who may be facing the loss of a limb or its normal functioning, I want to do that. You can see why it's easy for me to stay motivated."