Magnetic targeting increases mesenchymal stromal cell retention in lungs and enhances beneficial effects on pulmonary damage in experimental silicosis

Abstract

Silicosis is a pneumoconiosis caused by inhaled crystalline silica microparticles, which trigger inflammatory responses and granuloma formation in pulmonary parenchyma, thus affecting lung function. Although systemic administration of mesenchymal stromal cells (MSCs) ameliorates lung inflammation and attenuates fibrosis in experimental silicosis, it does not reverse collagen deposition and granuloma formation. In an attempt to improve the beneficial effects of MSCs, magnetic targeting (MT) has arisen as a potential means of prolonging MSC retention in the lungs. In this study, MSCs were incubated with magnetic nanoparticles and magnets were used for in vitro guidance of these magnetized MSCs and to enhance their retention in the lungs in vivo. In vitro assays indicated that MT improved MSC transmigration and expression of chemokine receptors. In vivo, animals implanted with magnets for 48 hours had significantly more magnetized MSCs in the lungs, suggesting improved MSC retention. Seven days after magnet removal, silicotic animals treated with magnetized MSCs and magnets showed significant reductions in static lung elastance, resistive pressure, and granuloma area. In conclusion, MT is a viable technique to prolong MSC retention in the lungs, enhancing their beneficial effects on experimentally induced silicosis. MT may be a promising strategy for enhancing MSC therapies for chronic lung diseases.

Application of magnetic nanoparticles in cell therapy

“…In addition, it was also important to minimize the injection dose, the toxicity and the side effects on healthy tissues and to cause the labeled cells or EVs to accumulate in the target tissue to reduce the in vitro administration concentration and frequency. As shown in Table 1, stem cells were labeled with MNPs and then injected into organisms under the magnetic field to treat lung injury [39], atrial fibrillation [61], coronary artery embolism [62], vascular diseases [63], systemic osteoporosis [36], retinitis [64], high intraocular pressure [30], Parkinson's disease [40,65], myocardial infarction [42] and spinal cord injury [43] and to regenerate articular cartilage and bone [66][67][68][69][70][71].…”

Micro/Nanosystems for Magnetic Targeted Delivery of Bioagents

“…Augmented cell retention led to a reduction in restenosis three weeks after cell delivery [268]. Magnetic targeting of mesenchymal stromal cells (MSCs) in the lungs was recently investigated [302]. In this study, MSCs were made magnetically responsive by incubation with citrate functionalized magnetic nanoparticles.…”

Mesenchymal stem/stromal cells as next-generation drug delivery vehicles for cancer therapeutics

“…Several studies demonstrated that the number of MSCs homing to the target site was increased by the loading of iron oxide NPs to MSCs and by applying the external magnetic field to the target site [35, [44][45][46][47]. In addition, several studies demonstrated that the expression of migration-related genes of MSCs were upregulated by only iron oxide NPs loading [44,48] or by the combination of the loading and application of the external magnetic field [49].…”