AAOS Exclusive: Nomenclature and Lack of Clinical Data Biggest Problems in Regenerative Medicine Research

The biggest problem right now in stem cell and regenerative medicine research, said George F. Muschler, M.D., at the 2014 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS) in New Orleans, La., is a name problem.

“One of the biggest problems in the field I would like addressed is nomenclature,” the Cleveland, Ohio-based Cleveland Clinic orthopedic surgeon said. “If I’ve got this stem cell from adipose tissue, and this from bone marrow, and this other one from an umbilical cord—to call them all stem cells, mesenchymal cells or anything—they’re all different We don’t have a nomenclature system that allows us to talk to one another.”

Two years ago at the Cleveland Clinic Summit 2012, Muschler expressed his frustration with the vagueness of regulation regarding stem cell products. As he noted above, stem cells are so different from one another, yet one product can gain 510(k) U.S. Food and Drug Administration (FDA) clearance based on another product that has set precedent, even though there are what Muschler would believe to be significant differences in the cells used. Then a third product would be cleared based in the second product’s precedent, and so on, making the potential for deviation high.

This problem with nomenclature affects regulation as well, Muschler told Orthopedic Design & Technology:

“The FDA is charged with both helping us avoid unsafe things and have some assurance of effectiveness. Faced with a stem cell bio world where there is a tremendous amount of challenges with nomenclature, the FDA is exerting itself on small group of entrepreneurial individuals who thought the data was good enough for them to just set up shop and grow cells—but the truth is, the [clinical] data is just not there to justify that. Wherever possible they shut down that activity.”

The lack of good existing clinical data on stem cell science is mainly due to the limiting nature of the infrastructure necessary to conduct such trials successfully, Muschler explained.

“The clinical infrastructure needed to do studies in cells is so different than with other kinds of studies,” Muschler said. “When it comes to cell studies, cells must be stored, transferred and implanted in the exact same way across trial centers. With other products, for instance joints or implants, they can be kept in buckets for months or years—cells are sensitive.”

Muschler was joined at this presentation by Thomas A. Einhorn, M.D., chairman of orthopedic surgery and professor of orthopedic surgery, biochemistry and biomedical engineering at Boston University (Mass.). His frustration lies in the disappointing trajectory of bone morphogenetic proteins (BMPs). BMPs (which are not stem cells, but were, 10 years ago, hoped to perform similar functions) are isolated and cloned from the demineralized extracellular matrix of adult bone, and are a growth factor used to grow bone and cartilage.¹ Medtronic Inc.’s Infuse Bone Graft/LT-Cage lumbar tapered fusion device is an example of a device that depends on BMPs, and it is designed to aid in the treatment of degenerative disc disease by helping cells grow around the implant to restore the degenerated disc space to its original height.

“In the last decade, BMPs were the promise of what growth factor would bring to us,” said Einhorn, who spend the early 2000s studying BMPs extensively. “I’m not yet ready to declare BMP a failure, but it hasn’t lived up to our hope. The next decade will focus on cell and stem cell biology. Stem cells could develop treatments for human injuries, and we can use stem cells as the basis for drug discovery research. Right now, stem cells used for cartilage and bone defects is gathering speed.”

Both Einhorn and Muschler were enthusiastic about one study that was presented at AAOS, which was, according to them, one of the most promising studies on stem cells yet. The study was funded by Osiris Therapeutics Inc., a Columbia, Md.-based regenerative medicine company which focuses on stem cells derived from bone marrow, and led by C. Thomas Vangsness Jr., M.D., of the Keck School of Medicine at the University of Southern California, Los Angeles, Calif.

“The study used hydrogel, a well-regulated delivery method,” said Einhorn. “ It used well accepted methods of of measuring pain. “The secondary outcomes were more interesting than the primary outcomes—the study suggested the potential for allogen stem cells that can be taken off the shelf and can be prepared for long term storage.”

“To our knowledge, this is the first randomized, double-blind, controlled study to evaluate the safety, regenerative effects and clinical outcomes of human mesenchymal stem cells delivered by intra-articular injection into the human knee,” wrote the researchers. “…Although there is a large body of preclinical research supporting the use of mesenchymal stem cells in the knee, to date, only very limited clinical data are available. There has been some research on the effects on articular cartilage degeneration, but this has predominantly been small, limited case reports or series on the administration of autologous cells from various sources.”

To read the entire study, click here.

References:

1.http://www.cgfr.co.uk/article/S1359-6101(96)00049-4/abstract