Biocompatibility and toxicity of magnetic nanoparticles in regenerative medicine

Regenerative medicine is a pioneering field aimed at restoring and regenerating the function of damaged cells, organs and tissues in order to establish normal function. It demands the cross communication of disciplines to develop effective therapeutic stem cell based therapies. Nanotechnology has been instrumental in the development and translation of basic research to the clinically relevant therapies. In particular, magnetic nanoparticles (MNPs) have been applied to tag, track and activate stem cells offering an effective means of monitoring in vitro and in vivo behaviour. MNPs are comprised of an iron oxide core with a biocompatible biological polymer. Safety is an issue of constant concern and emphasises on the importance of investigating the issue of toxicity. Any indication of toxicity can ultimately limit the therapeutic efficiency of the therapy. Toxicity is highly dependent on the physical, chemical and structural properties of the MNP itself as well as dose and intended use. Few in vitro studies have reported adverse effects of MNP on cells at in vitro in therapeutic doses. However, long term in vivo studies have not been studied as extensively. This review aims to summarise current research in this topic highlighting commonly used toxicity assays to investigate this.

[1]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[2]  R. Stephenson A and V , 1962, The British journal of ophthalmology.

[3]  Miss A.O. Penney (b) , 1974, The New Yale Book of Quotations.

[4]  R Weissleder,et al.  Superparamagnetic iron oxide: pharmacokinetics and toxicity. , 1989, AJR. American journal of roentgenology.

[5]  Jon Dobson,et al.  Structural and magnetic properties of nanoscale iron oxide particles synthesized in the presence of dextran or polyvinyl alcohol , 2001 .

[6]  W. Strober Trypan blue exclusion test of cell viability. , 2001, Current protocols in immunology.

[7]  Mathias Hoehn,et al.  Monitoring of implanted stem cell migration in vivo: A highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[8]  S. Cartmell,et al.  Development of magnetic particle techniques for long-term culture of bone cells with intermittent mechanical activation. , 2002, IEEE transactions on nanobioscience.

[9]  장윤희,et al.  Y. , 2003, Industrial and Labor Relations Terms.

[10]  Elliot R. McVeigh,et al.  Serial Cardiac Magnetic Resonance Imaging of Injected Mesenchymal Stem Cells , 2003, Circulation.

[11]  B. C. Saravanan,et al.  A rapid MTT colorimetric assay to assess the proliferative index of two Indian strains of Theileria annulata. , 2003, Veterinary parasitology.

[12]  C. Bárcena,et al.  APPLICATIONS OF MAGNETIC NANOPARTICLES IN BIOMEDICINE , 2003 .

[13]  Q. Pankhurst,et al.  Applications of magnetic nanoparticles in biomedicine , 2003 .

[14]  J. Frangioni,et al.  In Vivo Tracking of Stem Cells for Clinical Trials in Cardiovascular Disease , 2004, Circulation.

[15]  J. Dobson,et al.  Magnetic micro- and nanoparticle mediated activation of mechanosensitive ion channels. , 2005, Medical engineering & physics.

[16]  C. Berry Possible exploitation of magnetic nanoparticle–cell interaction for biomedical applications , 2005 .

[17]  Ajay Kumar Gupta,et al.  Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. , 2005, Biomaterials.

[18]  D. Ingber,et al.  Cellular mechanotransduction: putting all the pieces together again , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[19]  Teodoro Espinosa-Solares,et al.  Macroscopic mass and energy balance of a pilot plant anaerobic bioreactor operated under thermophilic conditions , 2006, Applied biochemistry and biotechnology.

[20]  Y. Ni,et al.  In vitro labeling and MRI of mesenchymal stem cells from human umbilical cord blood. , 2006, Magnetic resonance imaging.

[21]  Rong Zhou,et al.  Imaging stem cells implanted in infarcted myocardium. , 2006, Journal of the American College of Cardiology.

[22]  Chung-Yuan Mou,et al.  Bifunctional magnetic silica nanoparticles for highly efficient human stem cell labeling. , 2007, Nano letters.

[23]  Hossein Mozdarani,et al.  Study of apoptosis in labeled mesenchymal stem cells with superparamagnetic iron oxide using neutral comet assay. , 2007, Toxicology in vitro : an international journal published in association with BIBRA.

[24]  Dar-Ming Lai,et al.  Magnetic nanoparticle labeling of mesenchymal stem cells without transfection agent: Cellular behavior and capability of detection with clinical 1.5 T magnetic resonance at the single cell level , 2007, Magnetic resonance in medicine.

[25]  Mathias Getzlaff,et al.  Fundamentals of magnetism , 2007 .

[26]  J. Dobson,et al.  Development of Superparamagnetic Iron Oxide Nanoparticles (SPIONS) for Translation to Clinical Applications , 2008, IEEE Transactions on NanoBioscience.

[27]  C. Mason,et al.  A brief definition of regenerative medicine. , 2008, Regenerative medicine.

[28]  Aniruddh Solanki,et al.  Nanotechnology for regenerative medicine: nanomaterials for stem cell imaging. , 2008, Nanomedicine.

[29]  Clemens A van Blitterswijk,et al.  The effect of calcium phosphate microstructure on bone-related cells in vitro. , 2008, Biomaterials.

[30]  V. Dousset,et al.  How to trace stem cells for MRI evaluation? , 2008, Journal of the Neurological Sciences.

[31]  Chung-Yuan Mou,et al.  Internalization of mesoporous silica nanoparticles induces transient but not sufficient osteogenic signals in human mesenchymal stem cells. , 2008, Toxicology and applied pharmacology.

[32]  Jeff W M Bulte,et al.  In vivo MRI cell tracking: clinical studies. , 2009, AJR. American journal of roentgenology.

[33]  Jin-Kyu Lee,et al.  Dual-Modal Nanoprobes for Imaging of Mesenchymal Stem Cell Transplant by MRI and Fluorescence Imaging , 2009, Korean journal of radiology.

[34]  Jeong Ah Kim,et al.  The targeting of endothelial progenitor cells to a specific location within a microfluidic channel using magnetic nanoparticles , 2009, Biomedical microdevices.

[35]  L. Ferreira,et al.  Nanoparticles as tools to study and control stem cells , 2009, Journal of cellular biochemistry.

[36]  N. Barakat,et al.  Magnetically modulated nanosystems: a unique drug-delivery platform. , 2009, Nanomedicine.

[37]  Sharan Ramaswamy,et al.  Magnetic resonance imaging of chondrocytes labeled with superparamagnetic iron oxide nanoparticles in tissue-engineered cartilage. , 2009, Tissue engineering. Part A.

[38]  Rongjun Chen,et al.  The precise control of cell labelling with streptavidin paramagnetic particles. , 2009, Biomaterials.

[39]  166 FERUMOXIDES-PROTAMINE SULFATE IS MORE EFFECTIVE THAN FERUCARBOTRAN FOR CELL LABELING: IMPLICATIONS FOR CLINICALLY APPLICABLE CELL TRACKING USING MRI , 2009 .

[40]  Pauliina Lehtolainen,et al.  Magnetic tagging increases delivery of circulating progenitors in vascular injury. , 2009, JACC. Cardiovascular interventions.

[41]  Mauro Ferrari,et al.  Nanomedicine—Challenge and Perspectives , 2009 .

[42]  F. Franconi,et al.  Mesenchymal and neural stem cells labeled with HEDP-coated SPIO nanoparticles: In vitro characterization and migration potential in rat brain , 2009, Brain Research.

[43]  X. Montet,et al.  Superparamagnetic nanoparticles - a tool for early diagnostics. , 2010, Swiss medical weekly.

[44]  Yelena Katsenovich,et al.  Nanomedicine: magnetic nanoparticles and their biomedical applications. , 2010, Current medicinal chemistry.

[45]  N. Sniadecki A tiny touch: activation of cell signaling pathways with magnetic nanoparticles. , 2010, Endocrinology.

[46]  T. Park,et al.  Tracking of transplanted mesenchymal stem cells labeled with fluorescent magnetic nanoparticle in liver cirrhosis rat model with 3-T MRI. , 2010, Magnetic resonance imaging.

[47]  W. Moon,et al.  The effects of clinically used MRI contrast agents on the biological properties of human mesenchymal stem cells , 2010, NMR in biomedicine.

[48]  Morteza Mahmoudi,et al.  A new approach for the in vitro identification of the cytotoxicity of superparamagnetic iron oxide nanoparticles. , 2010, Colloids and surfaces. B, Biointerfaces.

[49]  K. Krishnan Biomedical Nanomagnetics: A Spin Through Possibilities in Imaging, Diagnostics, and Therapy , 2010, IEEE Transactions on Magnetics.

[50]  J. Joh,et al.  Characterization, in vitro cytotoxicity assessment, and in vivo visualization of multimodal, RITC-labeled, silica-coated magnetic nanoparticles for labeling human cord blood-derived mesenchymal stem cells. , 2010, Nanomedicine : nanotechnology, biology, and medicine.

[51]  Hon-Man Liu,et al.  Direct Labeling of hMSC with SPIO: the Long-Term Influence on Toxicity, Chondrogenic Differentiation Capacity, and Intracellular Distribution , 2011, Molecular Imaging and Biology.

[52]  M. O’Donnell,et al.  Multifunctional nanoparticles as coupled contrast agents. , 2010, Nature communications.

[53]  Alicia J El Haj,et al.  Controlled differentiation of human bone marrow stromal cells using magnetic nanoparticle technology. , 2010, Tissue engineering. Part A.

[54]  A. Keramane,et al.  Hyperpolarization of Human Mesenchymal Stem Cells in Response to Magnetic Force , 2010, IEEE Transactions on NanoBioscience.

[55]  D. Spray,et al.  Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and in vivo visualization by magnetic resonance imaging , 2011, Journal of nanobiotechnology.

[56]  Morteza Mahmoudi,et al.  Magnetic fluid hyperthermia: focus on superparamagnetic iron oxide nanoparticles. , 2011, Advances in colloid and interface science.

[57]  M. Mahmoudi,et al.  Protein-nanoparticle interactions: opportunities and challenges. , 2011, Chemical reviews.

[58]  M. Sahraian,et al.  Superparamagnetic iron oxide nanoparticles: promises for diagnosis and treatment of multiple sclerosis. , 2011, ACS chemical neuroscience.

[59]  Karthikeyan Subramani,et al.  Magnetic resonance imaging tracking of stem cells in vivo using iron oxide nanoparticles as a tool for the advancement of clinical regenerative medicine. , 2011, Chemical reviews.

[60]  Morteza Mahmoudi,et al.  Toxicity evaluations of superparamagnetic iron oxide nanoparticles: cell "vision" versus physicochemical properties of nanoparticles. , 2011, ACS nano.

[61]  B. Rashidian,et al.  Raman active jagged-shaped gold-coated magnetic particles as a novel multimodal nanoprobe. , 2011, Chemical communications.

[62]  Piotr Walczak,et al.  Tracking stem cells using magnetic nanoparticles. , 2011, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[63]  Vibha Rani,et al.  Nanotechnology: Emerging Tool for Diagnostics and Therapeutics , 2011, Applied biochemistry and biotechnology.

[64]  A. Ito,et al.  Tissue engineering using magnetite nanoparticles. , 2011, Progress in molecular biology and translational science.

[65]  S. Majumdar,et al.  Micrometer-sized iron oxide particle labeling of mesenchymal stem cells for magnetic resonance imaging-based monitoring of cartilage tissue engineering. , 2011, Magnetic resonance imaging.

[66]  S. Barcikowski,et al.  Comparison of nanoparticle-mediated transfection methods for DNA expression plasmids: efficiency and cytotoxicity , 2011, Journal of nanobiotechnology.

[67]  S. Gambhir,et al.  Noninvasive cell-tracking methods , 2011, Nature Reviews Clinical Oncology.

[68]  M. Wendland,et al.  Labeling human embryonic stem-cell-derived cardiomyocytes for tracking with MR imaging , 2011, Pediatric Radiology.

[69]  Taeghwan Hyeon,et al.  Mesoporous Silica-Coated Hollow Manganese Oxide Nanoparticles as Positive T1 Contrast Agents for Labeling and MRI Tracking of Adipose-Derived Mesenchymal Stem Cells , 2011, Journal of the American Chemical Society.

[70]  Martin Frenz,et al.  Metabolic pathway and distribution of superparamagnetic iron oxide nanoparticles: in vivo study , 2011, International journal of nanomedicine.

[71]  M. Alice Ottoboni,et al.  The dose makes the poison. , 2011, Nature nanotechnology.

[72]  Iseult Lynch,et al.  The evolution of the protein corona around nanoparticles: a test study. , 2011, ACS nano.

[73]  Тетяна Миколаївна Плохута,et al.  Application of magnetic nanoparticles in biomedicine , 2011 .

[74]  M. Mahmoudi,et al.  Superparamagnetic iron oxide nanoparticles (SPIONs): development, surface modification and applications in chemotherapy. , 2011, Advanced drug delivery reviews.

[75]  Orthopaedic applications of nanoparticle-based stem cell therapies , 2012, Stem Cell Research & Therapy.

[76]  Morteza Mahmoudi,et al.  Assessing the in vitro and in vivo toxicity of superparamagnetic iron oxide nanoparticles. , 2012, Chemical reviews.

[77]  W. Marsden I and J , 2012 .

[78]  Urs O. Häfeli,et al.  Crucial Ignored Parameters on Nanotoxicology: The Importance of Toxicity Assay Modifications and “Cell Vision” , 2012, PloS one.

[79]  Morteza Mahmoudi,et al.  Toxicity of Nanomaterials , 2012 .

[80]  F. Pu,et al.  Evaluation on cartilage morphology after intra-articular injection of titanium dioxide nanoparticles in rats , 2012 .

[81]  Daniel G. Anderson,et al.  Therapeutic angiogenesis using genetically engineered human endothelial cells. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[82]  M. Mahmoudi,et al.  Multifunctional stable fluorescent magnetic nanoparticles. , 2012, Chemical communications.

[83]  Junqiang Wang,et al.  Biocompatibility of nanoporous TiO 2 coating on NiTi alloy prepared via dealloying method , 2012 .

[84]  Henry Du,et al.  Gold nanoparticle-enhanced and size-dependent generation of reactive oxygen species from protoporphyrin IX. , 2012, ACS nano.

[85]  Y. Cohen,et al.  Mesenchymal stem cells induced to secrete neurotrophic factors attenuate quinolinic acid toxicity: A potential therapy for Huntington's disease , 2012, Experimental Neurology.

[86]  M. A. Clements,et al.  Efficient transfection of MG‐63 osteoblasts using magnetic nanoparticles and oscillating magnetic fields , 2014, Journal of tissue engineering and regenerative medicine.