Systematic Review Confirms Safety and Efficacy of Mesenchymal Stem Cells in Treating Disc Degeneration
Introduction: This systematic review is designed to assess the safety and efficacy of mesenchymal stromal/stem cells (MSCs) in the treatment of disc degeneration.
Methods: The researchers conducted a systematic review of peer-reviewed comparative controlled studies to assess the safety and efficacy of MSCs compared to no treatment/saline in animals and human subjects. A total of 24 animal studies met the inclusion criteria, 6 of which reported at least partial randomization of treatment. In these animal studies, 862 discs were treated with MSC injection, and 1,603 discs served as controls. The studies included both small animals (mouse, rat, and rabbit) and larger animals (sheep, dogs, and minipigs). None of the human trials met the inclusion criteria.
Results: Overall, MSC injection significantly inhibited disc degeneration, defined as restoration of disc height index similar to that of control discs and increased expression of proteoglycan or extracellular matrix genes. The majority of studies used bone marrow as the source of MSCs, but efficacy also was demonstrated in studies involving MSCs derived from synovial and adipose tissues. Bone-marrow-derived MSCs demonstrated superior quality of repair compared with other non-MSC treatments (eg, articular chondrocytes and mechanical distraction devices). A greater degree of degeneration was linked to greater efficacy of MSC injection.
The overall complication rate was 2.7%, and complications were only found in rabbit studies. These complications included osteophyte formation anterolaterally to the disc space, which was hypothesized to result from leakage of the MSCs.
Conclusion: MSCs were found to be safe and effective in animal models of disc degeneration. MSC injection increased disc space height in the majority of animal models evaluated in this review. The authors called for randomized clinical trials in humans.
As the practice of using mesenchymal stromal/stem cells (MSCs) to treat intervertebral disc degeneration increases, this article is a timely meta-analysis of the available literature on the safety and efficacy of such treatment.The review included 24 animal studies. Notably, there were no human studies that met the analysis criteria. There were only two human studies, conducted in 2010 and 2011, which were not blinded or contained a control group.
All three types of MSCs (bone marrow, synovial, and adipose) were found to be equally effective in treating disc degeneration with bone marrow being the better of the three. The complication rate was low at only 2.7%, with osteophyte formation along the anterolateral disc that was injected. Bone marrow-derived MSCs seem to have a latency period after being injected into a damaged intravertebral disc, and surprisingly seemed to be more effective in regeneration when the degree of degeneration was higher.
The authors point out that more human-based studies are needed as well as studies in higher animals. They correctly point out that human studies are handicapped by the lack of post-study histology and their relevancy on clinical and diagnostic (ie, MRI) follow-up.