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Stem cell therapy using mesenchymal stem/stromal cells (MSCs) represents a novel approach to treating severe diseases, including osteoarthritis. However, the therapeutic benefit of MSCs is highly dependent on their differentiation state, which can be regulated by many factors. Herein, three-dimensional (3D) magnetic scaffolds were successfully fabricated by incorporating magnetic nanoparticles (MNPs) into electrospun gelatin nanofibers. When positioned near a rotating magnet (f = 0.5 Hz), the magnetic scaffolds with the embedded MSCs were driven upward/downward in the culture container, which induced mechanical stimulation to MSCs due to spatial confinement and fluid flow. The extracellular matrix-mimicking scaffold and the alternating magnetic field significantly enhanced chondrogenesis instead of osteogenesis. Furthermore, the fiber topography could be tuned with different compositions of the coating layer on MNPs, and the topography had a significant impact on MSC differentiation. Selective up-regulation of chondrogenesis-related genes (COL2A1 and ACAN) was found for the magnetic scaffolds with citric acid-coated MNPs (CAG). In contrast, osteogenesis-related genes (RUNX2 and SPARC) were selectively and significantly up-regulated for the magnetic scaffolds with polyvinylpyrrolidone-coated MNPs. Prior to implantation in vivo, chondrogenic preconditioning of MSCs within the CAG scaffolds under a dynamic magnetic field resulted in superior osteochondral repair. Hence, the magnetic scaffolds together with an in-house rotating magnet device could be a novel platform to initiate multiple stimuli on stem cell differentiation for effective repair of osteochondral defects.

Chronic low-back pain of discal origin is linked strongly to disc degeneration. Current nonsurgical treatments are palliative and fail to restore the disc extracellular matrix. In this study the authors examined the capacity of ovine mesenchymal precursor cells (MPCs) to restore the extracellular matrix of degenerate discs in an ovine model.Three adjacent lumbar discs of 24 adult male sheep were injected intradiscally with chondroitinase-ABC (cABC) to initiate disc degeneration. The remaining lumbar discs were used as normal controls. Three months after cABC injection, the L3-4 discs of all animals were injected with either a high dose (4 × 10(6) cells, in 12 sheep) or low dose (0.5 × 10(6) cells, in 12 sheep) of MPCs suspended in hyaluronic acid (HA). The adjacent L4-5 degenerate discs remained untreated; the L5-6 discs were injected with HA only. The animals were euthanized at 3 or 6 months after MPC injections (6 sheep from each group at each time point), and histological sections of the lumbar discs were prepared. Radiographs and MR images were obtained prior to cABC injection (baseline), 3 months after cABC injection (pretreatment), and just prior to necropsy (posttreatment).Injection of cABC decreased the disc height index (DHI) of target discs by 45%-50%, confirming degeneration. Some recovery in DHI was observed 6 months after treatment in all cABC-injected discs, but the DHI increased to within baseline control values only in the MPC-injected discs. This improvement was accompanied by a reduction in MRI degeneration scores. The histopathology scores observed at 3 months posttreatment for the high-dose MPC-injected discs and at 6 months posttreatment for the low-dose MPC-injected discs were significantly different from those of the noninjected and HA-injected discs (p0.001) but not from the control disc scores.On the basis of the findings of this study, the authors conclude that the injection of MPCs into degenerate intervertebral discs can contribute to the regeneration of a new extracellular matrix.