Due to their regenerative capabilities, muscle-derived stem cells (MDSCs) may one day revolutionize the treatment of osteoarthritis (OA), potentially staving off the need for joint replacement surgery in millions of people, according to preliminary research presented Sunday at the annual meeting of the Orthopaedic Research Society in Chicago.

Animal studies suggest that MDSCs that are genetically engineered with bone morphogenic protein (BMP)-2 and BMP-4 and then placed in a scaffold will become osteoblasts within regenerated bone, according to Johnny Huard, PhD, director of the growth and development laboratory at Children's Hospital of Pittsburgh and associate professor in the departments of orthopaedic surgery and molecular genetics and biochemistry and engineering at the University of Pittsburgh School of Medicine in Pittsburgh. Moreover, the addition of vascular endothelial growth factor (VEGF) further promotes the bone healing mediated by BMPs, Dr. Huard says, primarily by promoting angiogenesis and improving cell survival.

"We are maybe 5 to 10 years away from applying this in the clinic [to repair] articular cartilage," Dr. Huard tells CIAOMed. "We have shown that the cells can differentiate toward chondrogenic lineages, and it is clear that we can use these cells to repair articular cartilage." If validated, he says, "the technology has the potential to stave off an OA epidemic."

Sex differences in stem cells

One interesting observation from stem cell reseach is that "male cells appear to be more primed to become bone and cartilage than female cells ... we are still looking for the reasons behind this," Dr. Huard says, adding that "these gender differences may help explain conflicting results in the literature on stem cells because people try to reproduce the results of other groups, but they don't pay attention to the gender of the animal. I think this is very important. Age is also a very important component, and we have not looked at this carefully yet, but we will," he says.

It is also important that researchers don't overlook the delivery vehicle when implanting stem cells, points out CIAOMed editorial board member Stephen Trippel, MD, professor of orthopaedic surgery at Indiana University school of medicine in Indianapolis, Indiana. "We are learning that the delivery vehicle need not be passive," he says. Progress is being made with the use of cell instructive polymers in this regard.

MDSCs can be used for more than bone and cartilage regeneration

Bone is not the only application of this technology, says Dr. Huard. Murine studies have shown that MDSCs can be useful for skeletal muscle repair after disease or injuries, including the damage caused by muscular dystrophy, cardiac repair following myocardial infarction, and preliminary research in spinal cord and nerve repair. In addition, there are ongoing human trials for urologic dysfunction. "We are taking muscle-derived cell technology from patients to reconstruct the bladder's sphincter," Dr. Huard tells CIAOMed. As many as 10 women have been implanted and "it's going pretty well; it is very safe, and some of the participants don't [experience leakage] any more." Since the MDSCs are derived from muscle biopsies taken from the same patient, there is no risk of rejection, making this a potentially very promising treatment.

Reference

1. Huard J, et al. Regenerative medicine based on muscle-derived stem cells: Potential applications for tissue regeneration and repair. Presented at: 52nd Annual Meeting of the Orthopaedic Research Society; March 18–22, 2006; Chicago, Ill. Workshop No. 1.