Science Translational Medicine: Transplant From Pigs Helps Regrow Human Muscle

People who have lost large amounts of muscle from traumatic accidents or military wounds can regrow these muscles with the help of a new procedure, researchers report in the 30 April issue of Science Translational Medicine.

The technique, developed by Stephen Badylak and Brian Sicari and colleagues at the University of Pittsburgh, uses an implanted biological scaffold made of extracellular matrix (ECM) from pigs to coax a person's own stem cells into becoming muscle cells. The extracellular matrix is a structure that in animals is made up primarily of proteins and carbohydrates. The matrix surrounds cells and gives them a nourishing environment.

After showing the ECM method worked in rodents with severely injured hind limbs, the researchers moved to treating five people who had lost between 58 and 90 percent of limb muscle.

All of the patients reported an improved quality of life, but the researchers measured a 25 percent functional improvement in three out of the five patients.

Treating patients with fresh wounds — soldiers soon after injury, for example — could make the technique even more effective. "The real benefits will come from being able to treat patients immediately," said Badylak.

Skeletal muscle can regenerate after an injury, but not in extreme situations called volumetric muscle loss, in which large amounts of muscle are destroyed. Treatments for volumetric muscle loss are limited, leaving patients struggling to perform day-to-day tasks.

 
 
Patient 5, who sustained a calf muscle injury, performs a single leg hop test before (above) and after the ECM procedure. The patient could hop three inches before the surgery, but was able to hop 34.5 inches six months after surgery. | Video courtesy of Drs. Elke Brown and Fabrisia Ambrosio

The five patients in the study were at least six months removed from the time of their injuries, and past surgeries and physical therapy had proved unsuccessful. Three of the patients were in the military; two had leg injuries from an improvised explosive device blast while one had an exercise-induced leg muscle injury. The other two patients were civilians with leg muscle injuries from skiing accidents.

Before surgery, all patients completed a customized, 12 to 16-week physical therapy program that focused specifically on their individual functional deficits. After plateauing in these regimens, with no signs of further improvement, each patient received the ECM scaffold surgical placement procedure.

The researchers removed the scar tissue in these patients and inserted the ECM material. "It's a pig extracellular matrix, but the molecules that make up the ECM are collagen, growth factors and other things. These types of factors are very important in biology," said Badylak during a 29 April teleconference for reporters.

Each patient immediately returned to their pre-surgical physical therapy regimen for another five to 23 weeks after the surgeries. The success of the surgeries was determined by their ability to improve at least 25 percent above their preoperative maximum ability in day-to-day activities. These activities included tasks like lifting a foot when walking, taking the stairs, getting out of a chair, and raising a leg to a sitting position. In the case of each patient, muscle grew, and the regrowth partially restored normal appearance.

Analyzing magnetic resonance and computed tomography images of the treated muscle, the researchers observed the formation of dense tissue at the implantation site at six months post-surgery. After implantation, the ECM scaffold material degrades and releases signaling molecules that attract stem cells to the site of injury.

These stem cells subsequently mature into muscle cells, leading to the development of brand new, healthy muscle tissue. The post-treatment physical therapy was critical for treatment effectiveness, the authors found. Physical therapy may trigger signals that direct stem cells toward becoming muscle cells rather than some other kind of cell, they proposed.