Pulsed electromagnetic field therapy, or pulsed signal therapy, has shown efficacy in treating many illnesses, including knee osteoarthritis. Although the mechanism is not fully understood, magnetic therapy is broadly welcomed because of its safe and noninvasive nature. At the cellular and molecular level, remote control of the cell fate by the magnetic field also has profound applications in both basic science and translational research. Here we demonstrate the use of pulsed electromagnetic field, one of the most benign and noninvasive extracellular cues, as a novel method to control specific chondrogenic differentiation of mesenchymal stem cells (MSCs). Chondrogenesis of transplanted MSCs inside the joint is considered one of the future therapies to rebuild the damaged cartilage. Here we show that pulsed electromagnetic field promotes chondrogenic differentiation of MSCs, and such a promoting effect can be drastically enhanced by the combined use of a magnetic hydrogel as the cell growth matrix. The magnetic hydrogel, synthesized by chemical cross-linking of gelatin and β-cyclodextrin and by embedding Fe3O4 magnetic nanoparticles in the hydrogel network, supports adhesion, growth, and proliferation of MSCs. Pulsed electromagnetic field boosts chondrogenesis of MSCs grown on the magnetic hydrogel, manifested by enhanced toluidine blue staining; higher expression of collagen II protein; and upregulation of collagen II, aggrecan, and SOX9 genes. Therefore, our work presents a robust method for chondrogenesis of MSCs using magnetic field as the external cue.
Keywords: bone marrow mesenchymal stem cell; cartilage regeneration; chondrogenesis; magnetic hydrogel; pulse electromagnetic field.