Noncellular material implanted in patients attracts stem cells to fix injuries
Badly injured patients can regrow lost muscle with help from implanted sheets of tissue from pigs. An experimental treatment worked well for three of five volunteers and showed some benefit in a fourth, researchers report in the April 30 Science Translational Medicine.
“This is five patients, and that’s not huge. But it’s a benchmark,” says George Christ, a physiologist at Wake Forest School of Medicine in Winston-Salem, N.C., who wasn’t involved in this study. “It’s good to see studies out there trying to address this huge gap in medical knowledge and treatment.”
Although muscle can regenerate after trauma, large-volume losses of the tissue don’t fully recover. To encourage regrowth, the scientists used pig bladder tissue with all of its cells removed, leaving a sterilized matrix sheet of collagen and many other compounds common to mammals. Implanted in sites of muscle loss in mice, the material gave off chemical signals that attracted stem cells from elsewhere in the body. The tissue sheets also served as a physical scaffold on which those cells grew and took on characteristics of muscle cells, says study coauthor Brian Sicari, a researcher at the University of Pittsburgh School of Medicine.
A larger, multilayer version of this scaffold was implanted in five men, including two military servicemen who were injured by explosive devices and another hurt while exercising. The two other patients were civilians who had been in serious accidents. All five had lost considerable muscle tissue in either the thigh or lower leg and had endured physical therapy and various surgeries to remove scar tissue in failed attempts to regrow lost muscle. Their injuries had occurred one to seven years before the study.
“Most of these patients have been through hell,” says coauthor Stephen Badylak, a physician and researcher also at Pittsburgh. A day or two after undergoing surgery to implant a sheet of the scaffold material at the injury site, all five went into rigorous physical therapy. Such movement, Badylak says, instructs stem cells homing to the scaffold’s chemical cues that they should become muscle cells. Biopsies of the implant site showed muscle regrowth in all five patients.
Each patient also underwent tests of everyday movements such as getting up from a chair, standing balanced on the injured leg with eyes closed, jumping on that leg, squatting or reaching forward and backward while standing. Three patients passed all tests relevant to their injury 24 to 28 weeks after implantation. Another patient passed six of seven tests but failed a standing balance test. Although one patient experienced little physical improvement, Badylak says this is the first study to show this degree of regrowth in multiple people with extensive muscle loss.
The material used in the sheets offers good niches for cells to grow in because it is originally made by cells, he says. What’s more, the matrix sheets start to degrade once implanted. As they do, Badylak says, the proteins break down into peptides that benefit muscle growth and spur blood vessel formation to nourish that recovery.
Badylak hopes to further test the treatment on up to 80 people with muscle-loss injuries.
B.M. Sicari et al. An acellular biologic scaffold promotes skeletal muscle formation in mice and humans with volumetric muscle loss. Science Translational Medicine. Vol. 6, April 30, 2014, p. 234ra58. doi: 10.1126/scitranslmed.3008085.
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B.T. Corona et al. Further development of a tissue engineered muscle repair construct in vitro for enhanced functional recovery following implantation in vivo in a murine model of volumetric muscle loss injury. Tissue Engineering Part A. Vol. 18, June 2012, p. 1213.