Abstract
IntroductionSynovial mesenchymal stem cells (MSCs) have high proliferative and chondrogenic potentials, and MSCs transplanted into the articular cartilage defect produce abundant extracellular matrix. Because of similarities between the articular cartilage and the intervertebral disc cartilage, synovial MSCs are a potential cell source for disc regeneration. Here, we examined the effect of intradiscal transplantation of synovial MSCs after aspiration of nucleus pulposus in rabbits.MethodsThe nucleus pulposus tissues of rabbit's intervertebral discs were aspirated to induce disc degeneration, and allogenic synovial MSCs were transplanted. At 2, 4, 6, 8, 16, 24 weeks postoperatively, we evaluated with imaging analyses such as X-ray and magnetic resonance imaging (MRI), and histological analysis. To investigate interaction between synovial MSCs and nucleus pulposus cells, human synovial MSCs and rat nucleus pulposus cells were co-cultured, and species specific microarray were performed.ResultsThe existence of transplanted cells labeled with DiI or derived from green fluorescent protein (GFP)-expressing transgenic rabbits was confirmed up until 24 weeks. X-ray analyses demonstrated that intervertebral disc height in the MSC group remained higher than that in the degeneration group. T2 weighted MR imaging showed higher signal intensity of nucleus pulposus in the MSC group. Immunohistological analyses revealed higher expression of type II collagen around nucleus pulposus cells in the MSC group compared with even that of the normal group. In co-culture of rat nucleus pulposus cells and human synovial MSCs, species specific microarray revealed that gene profiles of nucleus pulposus were altered markedly with suppression of genes relating matrix degradative enzymes and inflammatory cytokines.ConclusionsSynovial MSCs injected into the nucleus pulposus space promoted synthesis of the remaining nucleus pulposus cells to type II collagen and inhibition of expressions of degradative enzymes and inflammatory cytokines, resulting in maintaining the structure of the intervertebral disc being maintained.
Highlights
Synovial mesenchymal stem cells (MSCs) have high proliferative and chondrogenic potentials, and MSCs transplanted into the articular cartilage defect produce abundant extracellular matrix
We demonstrated that synovial MSCs expanded faster than bone marrow MSCs when cultured with 10% human autologous serum [15]
As MSCs are defined by adherence to plastic and trilineage differentiation [20], our results indicate that the rabbit synovium-derived cells had characteristics of MSCs
Summary
Synovial mesenchymal stem cells (MSCs) have high proliferative and chondrogenic potentials, and MSCs transplanted into the articular cartilage defect produce abundant extracellular matrix. We examined the effect of intradiscal transplantation of synovial MSCs after aspiration of nucleus pulposus in rabbits. The nucleus pulposus of normal disc includes sparse chondrocytes surrounded by extracellular matrix which mainly consist of type II collagen and proteoglycan. It functions as a shock absorber against mechanical load due to its highly hydrophilic structure. Some reports have demonstrated that transplantation of bone marrow mesenchymal stem cells (MSCs) delayed degeneration of the nucleus pulposus [8,9,10]
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