Overselling Stem Cells?

This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.

In orthopaedics, the term “biologics” is often applied to cell-based therapies. There are a number of centers using mesenchymal stem cells (MSCs) in musculoskeletal medicine, and a recent systematic review assessed the quality of literature and procedural specifics surrounding MSC therapy for osteoarthritis (OA)¹.

The authors searched four large scientific databases for studies investigating MSCs for OA treatment. Among the 61 articles analyzed, 2,390 OA patients were treated, most with adipose-derived stem cells (ADSCs) (n = 29 studies) or bone marrow-derived stem cells (BMSCs) (n = 30 studies), though the preparation techniques varied within each group. In a subanalysis of 5 Level I and 9 Level II studies (288 patients), researchers found that 8 studies used BMSCs, 5 used ADSCs, and 1 used peripheral blood stem cells. A risk-of-bias analysis showed 5 Level I studies at low risk, 7 Level II studies at moderate risk, and 2 Level II studies at high risk. The authors concluded that although there is a “notion” that MSC therapy has a positive effect on OA patients, there is limited high-quality evidence and a dearth of long-term follow-up.

Despite the low-quality evidence and the many questions surrounding MSCs for treating OA, there are an estimated 570 clinics in the US marketing “stem cell” treatments for orthopaedic problems². The American Academy of Orthopaedic Surgeons (AAOS) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases recently convened a symposium on this issue. According to Constance Chu, MD, professor of orthopaedic surgery at Stanford University and the symposium program chair, the objective was to establish a clear, collective impact agenda for the clinical evaluation, use, and optimization of biologics in orthopaedics, and to develop a guidance document on clinically meaningful endpoints and outcome metrics for the evaluation of biologics used in orthopaedics.

Symposium attendees examined the possible use of registries to generate clinical evidence on the use of biologics in orthopaedics. Registry models that could be employed to obtain data on practice patterns and early warning of potential issues include the American Joint Replacement Registry, the Kaiser Registry, and the International Cartilage Repair Registry. Another model could be a biorepository-linked registry similar to what has been established at the VA Hospital in Palo Alto, California, where samples from platelet-rich plasma are stored for later comparison with clinical outcomes.

References

1. Jevotovsky DS, Alfonso AR, Einhorn TA, Chiu ES. Osteoarthritis and Stem Cell Therapy in Humans: A Systematic Review, Osteoarthritis and Cartilage (2018), doi: 10.1016/ j.joca.2018.02.906.
2. Symposium by The American Academy of Orthopaedic Surgeons and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. “Optimizing Clinical Use of Biologics in Orthopaedic Surgery,” Feb. 15–17, 2018, at Stanford University.