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Lineage-related and particle size-dependent cytotoxicity of chitosan nanoparticles on mouse bone marrow-derived hematopoietic stem and progenitor cells
Affiliation:1. Drug Delivery and Novel Targeting Research Group, Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia;2. Program of Biomedical Science, School of Diagnostic and Applied Health Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia;1. Microelectronics Research Center, Department of Electrical and Computer Engineering, Iowa State University, Ames, IA 50011, USA;2. Department of Physics and Astronomy and Ames Laboratory, Iowa State University, Ames, IA 50011, USA;3. Lightwave Power, 57 Smith Place, Cambridge, MA 02138, USA;1. Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People''s Hospital, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, 600 Yishan Road, Shanghai, China;1. Department of Pathology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran;2. Department of Anatomical Sciences, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran;3. Solid Tumor Research Center, Urmia University of Medical Sciences, Urmia, Iran;4. Department of Surgery and Diagnostic Imaging, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran;1. Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA;2. Lawrence Livermore National Laboratory, Livermore, CA 94550, USA;3. Centre for Energy Research, Hungarian Academy of Sciences, H-1525 Budapest, Hungary
Abstract:Chitosan nanoparticles (CSNPs) have potential applications in stem cell research. In this study, ex vivo cytotoxicity of CSNPs on mouse bone marrow-derived (MBMCs) hematopoietic stem and progenitor cells (HSPCs) was determined. MBMCs were exposed to CSNPs of different particle sizes at various concentrations for up to 72 h. Cytotoxicity effect of CSNPs on MBMCs was determined using MTT, Live/Dead Viability/Cytotoxicity assays and flow cytometry analysis of surface antigens on HSCs (Sca-1+), myeloid-committed progenitors (CD11b+, Gr-1+), and lymphoid-committed progenitors (CD45+, CD3e+). At 24 h incubation, MBMCs' viability was not affected by CSNPs. At 48 and 72 h, significant reduction was detected at higher CSNPs concentrations. Small CSNPs (200 nm) significantly reduced MBMCs' viability while medium-sized particle (∼400 nm) selectively promoted MBMCs growth. Surface antigen assessment demonstrated lineage-dependent effect. Significant decrease in Sca-1+ cells percentage was observed for medium-sized particle at the lowest CSNPs concentration. Meanwhile, reduction of CD11b+ and Gr-1+ cells percentage was detected at high and intermediate concentrations of medium-sized and large CSNPs. Percentage of CD45+ and CD3e+ cells along with ROS levels were not significantly affected by CSNPs. In conclusion, medium-sized and large CSNPs were relatively non-toxic at lower concentrations. However, further investigations are necessary for therapeutic applications.
Keywords:Nanomaterials  Chitosan  Nanocytotoxicity  Aggregation  Hematopoietic stem cells  Lineage-committed progenitors  CSNPs"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0045"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Chitosan nanoparticles  DHE"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0055"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  dihydroethidium  FITC"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0065"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  fluorescein isothiocyanate  hydrogen peroxide  HE"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0085"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  hydroethidine  HSPCs"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0095"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  hematopoietic stem and progenitor cells  MBMCs"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0105"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  mouse bone marrow-derived  MTT"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0115"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide  PDI"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0125"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  polydispersity index  RNAi"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0135"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  RNA interfering  ROS"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0145"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  reactive oxygen species  TPP"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0155"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  tripolyphosphate
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