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Effects of Static Magnetic Fields on Natural or Magnetized Mesenchymal Stromal Cells: Repercussions for Magnetic Targeting
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A2924 - Effects of Static Magnetic Fields on Natural or Magnetized Mesenchymal Stromal Cells: Repercussions for Magnetic Targeting
Author Block: F. F. Cruz1, L. H. A. Silva1, S. M. Silva2, E. C. D. Lima2, R. C. Silva3, D. J. Weiss4, M. Morales5, P. R. Rocco5; 1Federal University of Rio De Janeiro, Rio de Janeiro, Brazil, 2Institute of Chemistry, Federal University of Goiás, Goiania, Brazil, 3National Institute of Metrology, Quality and Technology (InMetro), Rio de Janeiro, Brazil, 4Univ of Vermont/Hlth Sci Rsch Facility, Burlington, VT, United States, 5Federal University of Rio De Janeiro, Rio De Janeiro, Brazil.
RATIONALE: Despite much investigation, mesenchymal stromal cell (MSC)-based therapies have not yet demonstrated efficacy in clinical trials. Among the many factors involved, systemically administered MSCs lodge in the lung and are then rapidly cleared, hindering delivery to target sites. In this context, the magnetic targeting (MT) technique has emerged as a strategy to improve MSC delivery. However, the moderate-intensity static magnetic fields (SMFs) used for MT may exert effects of their own on MSCs. Thus, we aimed to evaluate the effects of SMF on MSCs in vitro and their application in vivo. METHODS: Cells were initially magnetized using citrate-coated magnetite nanoparticles. Then, control and magnetized MSCs were transferred to an in vitro MT system and exposed to 0.3-0.45 Tesla SMFs. MSC viability, morphology, ultrastructure, proliferation rates, differentiation, and immunomodulation were evaluated after 24 and 48 hours of exposure. Magnetic targeting was then tested with magnetized MSCs in a murine model of acute lung injury. RESULTS: In the in vitro model of magnetic targeting used herein, MSCs exposed to static magnetic fields (intensity 0.3-0.45 Tesla) exhibited significant reductions in viability after 48 hours. This effect was time-dependent. Although viability loss was observed in magnetized and non-magnetized MSCs alike, exposure to iron oxide nanoparticles seemed to aggravate this effect. Viability loss may be secondary to plasma membrane changes and to oxidative effects induced by magnetic fields. However, the morphology, proliferation, and differentiation capacity of MSCs remained unchanged. Importantly, these MSCs remained functional, able to secrete anti-inflammatory and repair mediators and modulate expression of alveolar macrophage genes, an important element of innate immunity. More cells were found in the lungs exposed to magnetic fields in vivo, resulting in improvement of lung mechanics and reduction in inflammation. CONCLUSION: The experimental protocol tested herein is a promising alternative and should be applied in future in vivo MT studies.
Author Block: F. F. Cruz1, L. H. A. Silva1, S. M. Silva2, E. C. D. Lima2, R. C. Silva3, D. J. Weiss4, M. Morales5, P. R. Rocco5; 1Federal University of Rio De Janeiro, Rio de Janeiro, Brazil, 2Institute of Chemistry, Federal University of Goiás, Goiania, Brazil, 3National Institute of Metrology, Quality and Technology (InMetro), Rio de Janeiro, Brazil, 4Univ of Vermont/Hlth Sci Rsch Facility, Burlington, VT, United States, 5Federal University of Rio De Janeiro, Rio De Janeiro, Brazil.
RATIONALE: Despite much investigation, mesenchymal stromal cell (MSC)-based therapies have not yet demonstrated efficacy in clinical trials. Among the many factors involved, systemically administered MSCs lodge in the lung and are then rapidly cleared, hindering delivery to target sites. In this context, the magnetic targeting (MT) technique has emerged as a strategy to improve MSC delivery. However, the moderate-intensity static magnetic fields (SMFs) used for MT may exert effects of their own on MSCs. Thus, we aimed to evaluate the effects of SMF on MSCs in vitro and their application in vivo. METHODS: Cells were initially magnetized using citrate-coated magnetite nanoparticles. Then, control and magnetized MSCs were transferred to an in vitro MT system and exposed to 0.3-0.45 Tesla SMFs. MSC viability, morphology, ultrastructure, proliferation rates, differentiation, and immunomodulation were evaluated after 24 and 48 hours of exposure. Magnetic targeting was then tested with magnetized MSCs in a murine model of acute lung injury. RESULTS: In the in vitro model of magnetic targeting used herein, MSCs exposed to static magnetic fields (intensity 0.3-0.45 Tesla) exhibited significant reductions in viability after 48 hours. This effect was time-dependent. Although viability loss was observed in magnetized and non-magnetized MSCs alike, exposure to iron oxide nanoparticles seemed to aggravate this effect. Viability loss may be secondary to plasma membrane changes and to oxidative effects induced by magnetic fields. However, the morphology, proliferation, and differentiation capacity of MSCs remained unchanged. Importantly, these MSCs remained functional, able to secrete anti-inflammatory and repair mediators and modulate expression of alveolar macrophage genes, an important element of innate immunity. More cells were found in the lungs exposed to magnetic fields in vivo, resulting in improvement of lung mechanics and reduction in inflammation. CONCLUSION: The experimental protocol tested herein is a promising alternative and should be applied in future in vivo MT studies.
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