Abstract
IntroductionMesenchymal stem cells (MSCs) are widely considered to hold promise for the treatment of intervertebral disc (IVD) degeneration. However, variation in the therapeutic efficacy of MSCs is a major problem and the derivation of MSCs for use in IVD regeneration has not been optimized. Additionally, no data are available on the efficacy of Wharton’s Jelly-derived MSC (WJ-MSC) transplantation in an animal model of IVD degeneration.MethodsThis study evaluated the effectiveness of a cross-linked hyaluronic acid (XHA) scaffold loaded with human WJ-MSCs, according to their expression levels of transforming growth factor-β receptor I/activin-like kinase receptor 5 (TβRI/ALK5) and TβRII, for IVD regeneration in a rabbit model. We compared the degree of IVD regeneration between rabbits transplanted with a XHA scaffold loaded with WJ-MSCs highly and lowly expressing TβRI/ALK5 and TβRII (MSC-highTR and MSC-lowTR, respectively) using magnetic resonance imaging (MRI) and histological analysis.ResultsAt 12 weeks after transplantation, T2-weighted MRI analysis showed significant restoration of the disc water content in rabbits treated with a MSC-highTR-loaded XHA scaffold in comparison to rabbits treated with the scaffold alone or a MSC-lowTR-loaded XHA scaffold. In addition, morphological and histological analyses revealed that IVD regeneration was highest in rabbits transplanted with a MSC-highTR-loaded XHA scaffold.ConclusionTaken together, our results suggest that a MSC-highTR-loaded XHA scaffold supports IVD regeneration more effectively than a MSC-lowTR-loaded XHA scaffold. This study supports the potential clinical use of MSC-highTR-loaded XHA scaffolds to halt IVD degeneration or to enhance IVD regeneration.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0183-1) contains supplementary material, which is available to authorized users.
Highlights
Mesenchymal stem cells (MSCs) are widely considered to hold promise for the treatment of intervertebral disc (IVD) degeneration
Variation in the expression levels of TβRI/Activin-like kinase receptor 5 (ALK5) and TβRII in Wharton’s Jelly-derived MSC (WJ-MSC) among donors fluorescenceactivated cell sorting (FACS) analysis showed that the expression levels of TβRI/ ALK5 and TβRII in WJ-MSCs from different donors differed among the donors
The expression of growth differentiation factor-15 (GDF-15) and matrix metalloproteinase-1 (MMP-1) was much higher in MSC-highTR than in MSClowTR, whereas expression of chemokine (C-C motif) ligand 5 (CCL-5) was much higher in MSC-lowTR than in MSC-highTR. These results suggested that the expression levels of TβRI/ALK5 and TβRII in WJ-MSCs could influence their secretion of cytokines such as GDF-15, MMP-1, and Chemokine ligand 5 (CCL-5) and their response to autocrine Transforming growth factor beta (TGFβ) ligands and that WJ-MSCs could improve IVD degeneration by releasing paracrine factors
Summary
Mesenchymal stem cells (MSCs) are widely considered to hold promise for the treatment of intervertebral disc (IVD) degeneration. Variation in the therapeutic efficacy of MSCs is a major problem and the derivation of MSCs for use in IVD regeneration has not been optimized. No data are available on the efficacy of Wharton’s Jelly-derived MSC (WJ-MSC) transplantation in an animal model of IVD degeneration. In animal models of IVD degeneration, mesenchymal stem cells (MSCs) from different sources have shown promising results in regenerating degenerated IVD. Variation in the therapeutic efficacy of MSCs due to their different differentiation capacity is one of the major problems. With regards to improving the therapeutic potential of transplanted MSCs, a scaffolding technology is considered to be important to prevent cell leakage and reduce the risk of uncontrolled MSC differentiation into osteoclasts leading to osteophyte formation. Rabbits exhibit osteophyte growth in the anterolateral disc space due to cell leakage after MSC transplantation [20, 21]
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