Fe3O4/BSA particles induce osteogenic differentiation of mesenchymal stem cells under static magnetic field

Acta Biomater. 2016 Dec:46:141-150. doi: 10.1016/j.actbio.2016.09.020. Epub 2016 Sep 16.

Abstract

Differentiation of stem cells is influenced by many factors, yet uptake of the magnetic particles with or without magnetic field is rarely tackled. In this study, iron oxide nanoparticles-loaded bovine serum albumin (BSA) (Fe3O4/BSA) particles were prepared, which showed a spherical morphology with a diameter below 200 nm, negatively charged surface, and tunable magnetic property. The particles could be internalized into bone marrow mesenchymal stem cells (MSCs), and their release from the cells was significantly retarded under external magnetic field, resulting in almost twice intracellular amount of the particles within 21 d compared to that of the magnetic field free control. Uptake of the Fe3O4/BSA particles enhanced significantly the osteogenic differentiation of MSCs under a static magnetic field, as evidenced by elevated alkaline phosphatase (ALP) activity, calcium deposition, and expressions of collagen type I and osteocalcin at both mRNA and protein levels. Therefore, uptake of the Fe3O4/BSA particles brings significant influence on the differentiation of MSCs under magnetic field, and thereby should be paid great attention for practical applications.

Statement of significance: Differentiation of stem cells is influenced by many factors, yet uptake of the magnetic particles with or without magnetic field is rarely tackled. In this study, iron oxide nanoparticles-loaded bovine serum albumin (BSA) (Fe3O4/BSA) particles with a diameter below 200nm, negatively charged surface, tunable Fe3O4 content and subsequently adjustable magnetic property were prepared. The particles could be internalized into bone marrow mesenchymal stem cells (MSCs), and their release from the cells was significantly retarded under external magnetic field. Uptake of the Fe3O4/BSA particles enhanced significantly the osteogenic differentiation of MSCs under a constant static magnetic field, while the magnetic particles and external magnetic field alone do not influence significantly the osteogenic differentiation potential of MSCs regardless of the uptake amount. The results demonstrate a potential magnetic manipulation method for stem cell differentiation, and also convey the significance of careful evaluation of the safety issue of magnetic particles in real an application situation.

Keywords: Cell differentiation; Cellular uptake; Magnetic field; Magnetic particles; Mesenchymal stem cell.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Blotting, Western
  • Calcium / metabolism
  • Cattle
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Collagen Type I / metabolism
  • Endocytosis / drug effects
  • Ferric Compounds / pharmacology*
  • Gene Expression Regulation / drug effects
  • Magnetic Fields*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / enzymology
  • Models, Biological
  • Osteocalcin / metabolism
  • Osteogenesis / drug effects*
  • Particle Size
  • Rats, Sprague-Dawley
  • Serum Albumin, Bovine / pharmacology*
  • Thermogravimetry

Substances

  • Collagen Type I
  • Ferric Compounds
  • Osteocalcin
  • ferric oxide
  • Serum Albumin, Bovine
  • Alkaline Phosphatase
  • Calcium