Implanted Synovial Mesenchymal Stem Cells Prevent Intervertebral Disc Degeneration in Rabbit Model
Introduction: Previous studies have demonstrated that synovial mesenchymal stem cells (MSC) implanted into damaged articular cartilage produce an extracellular matrix. Given that articular cartilage and intervertebral disc cartilage are similar histologically and biochemically, this study examined whether transplantation of synovial MSC into the intradiscal space delayed disc degeneration in a rabbit model.
Methods: The researchers aspirated the nucleus pulposus tissues from rabbits’ intervertebral discs to create a model of disc degeneration. Allogenic synovial MSCs were extracted and implanted into the intervertebral space. The rabbits were evaluated up to 24 weeks postoperatively. In addition, to understand the interaction between synovial MSCs and nucleus pulposus cells, the researchers co-cultured human synovial MSCs and rat nucleus pulposus cells and performed species-specific microarray.
Results: Maintenance of transplanted cells was confirmed up to 24 weeks. MSC implantation was associated with greater intervertebral disc higher compared with control discs that were aspirated and untreated. The MSC implanted discs also showed a greater expression of type II collagen around remaining nucleus pulposus cells as early as 2 weeks postoperatively compared with discs that were approached but not aspirated or treated. Magnetic resonance imaging suggested that the effects of MSCs started to decrease by 6 weeks. In the co-culture of rat nucleus pulposus cells and human synovial MSCs, RNA isolated from the cultured cells revealed that the gene profiles of the nucleus pulposus cells were altered markedly (ie, genes relating to matrix degradative enzymes and inflammatory cytokines were suppressed).
Conclusion: Transplantation of synovial MSCs into a rabbit model of intervertebral disc degeneration showed efficacy in preventing disc degeneration up to 24 weeks. The authors believe that the higher amount of type II collagen produced by the transplanted MSCs acted as a framework in the nucleus pulposus, which allowed for maintenance of disc height and histological features.
Various autograft types of MSCs (eg, cells derived from bone marrow and adipose tissue) have been looked at as a possible source for intravertebral disc regeneration in both in vitro and in vivo studies. The authors claim that this paper is the first to demonstrate the effectiveness of synovial MSCs to have a positive regenerative effect in an in vivo animal model of intravertebral disc degeneration.
The authors noted that species differences might explain the positive effects of MSC injection, since rabbits discs contain more notochordal cells than human discs. Notochordal cells have been shown to play a crucial role in disc regeneration.
Second, synovial MSCs seem to have a similar preventive/regenerative effect as bone marrow MSCs; hence, since synovial MSCs can be expanded faster than bone marrow MSCs, they should be considered an attractive alternative, the authors suggested. That said, the harvesting of synovial MSCs might be more troublesome than bone marrow MSCs in real-life clinical practice.
Finally, while synovial MSCs had positive effects on nucleus pulposus cell gene expression (eg, increased type 2 collagen synthesis, increased chondroitin sulfate proteoglycan 2 expression, and down regulation of inflammatory cytokines and degradative enzymes), MSCs did not show an altered gene profile when cultured with nucleus pulposus cells.