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Magnetic Targeting of MSCs Improves Treatment of Lung Disease

Review of “Magnetic targeting increases mesenchymal stromal cell retention in lungs and enhances beneficial effects on pulmonary damage in experimental silicosis” from STEM CELLS Translational Medicine by Stuart P. Atkinson

In the long-term lung disease silicosis, inhaled crystalline silica microparticles trigger an inflammatory response and granuloma formation in the pulmonary parenchyma, thus impairing lung function [1]. Mesenchymal stem cell (MSC) therapy has demonstrated efficacy as a treatment for silicosis in preclinical models [2]; however, while analysis using murine models has established that systemically-administered MSCs can reduce inflammation and fibrosis, this treatment approach failed to reverse collagen deposition and granuloma formation [3].

Recent research from the laboratory of Patricia R. M. Rocco (Universidade Federal do Rio de Janeiro, Brazil) sought to discover whether magnetic targeting of MSCs could prolong lung retention and thereby enhance the beneficial effects of MSC therapy, given the success of this approach in preclinical models of joint, spinal cord, and cardiac injuries [4]. In their new STEM CELLS Translational Medicine article, Silva et al. now report that the magnetic targeting of MSCs to the lungs of a silicosis mouse model provides for significantly enhanced therapeutic outcomes [5].

Beginning with in vitro analysis, the authors first confirmed their previously published similar study [6] by demonstrating the magnetic responsivity and viability of MSCs labeled with superparamagnetic citrate‐capped maghemite nanoparticles [7] and then establishing that magnetic targeting improves MSC migration through a transwell system towards silica‐activated alveolar macrophages. Interestingly, the authors also discovered that the magnetic field employed enhanced the expression of genes related to MSC adhesion and chemotaxis to contribute to the observed improvements in transmigration. Therefore, any improvements to MSC therapy may be due to the combination of enhanced targeting and magnetic field-induced phenotypic alterations.

Moving in vivo, the authors next demonstrated that silicosis model mice with magnets placed over the chest area for 48 hours displayed enhanced levels of lung retention after the intravenous administration of labeled MSCs when compared to non-labeled MSCs. Encouragingly, assessments made at seven days after the removal of the magnets revealed significant improvements to silicosis symptoms, with improvements observed in both lung mechanics (reduced static lung elastance and resistive pressure) and granuloma area, but not in collagen deposition. Lung tissues in magnetically-targeted silicosis model mice also displayed reduced levels of the pro‐inflammatory cytokine interleukin (IL)‐1β, increased levels of the anti‐inflammatory cytokine IL‐10, and reduced mRNA expression of types I and III procollagen. 

In summary, these exciting findings support the implementation of magnetic targeting to improve MSC therapy for a range of conditions. Furthermore, magnetic targeting will likely form part of the next generation of cell therapies that aim to reverse collagen deposition and provide for improved therapeutic outcomes in silicosis patients.

For more on the massive potential of magnetically targeted MSC therapy, stay tuned to the Stem Cells Portal!

References

  1. Leung CC, Yu ITS, and Chen W, Silicosis. The Lancet 2012;379:2008-2018.
  2. Lopes-Pacheco M, Bandeira E, and Morales MM, Cell-based therapy for silicosis. Stem Cells International 2016;2016.
  3. Bandeira E, Oliveira H, Silva JD, et al., Therapeutic effects of adipose-tissue-derived mesenchymal stromal cells and their extracellular vesicles in experimental silicosis. Respiratory Research 2018;19:104.
  4. Silva LHA, Cruz FF, Morales MM, et al., Magnetic targeting as a strategy to enhance therapeutic effects of mesenchymal stromal cells. Stem Cell Research & Therapy 2017;8:58.
  5. Silva LHA, Silva MC, Vieira JB, et al., Magnetic targeting increases mesenchymal stromal cell retention in lungs and enhances beneficial effects on pulmonary damage in experimental silicosis. STEM CELLS Translational Medicine 2020;9:1244-1256.
  6. Silva LHA, da Silva JR, Ferreira GA, et al., Labeling mesenchymal cells with DMSA-coated gold and iron oxide nanoparticles: assessment of biocompatibility and potential applications. Journal of Nanobiotechnology 2016;14:59.
  7. Silva LHA, Silva SM, Lima ECD, et al., Effects of static magnetic fields on natural or magnetized mesenchymal stromal cells: Repercussions for magnetic targeting. Nanomedicine: Nanotechnology, Biology and Medicine 2018;14:2075-2085.