Control of smooth muscle α-actin (SMA) up-regulation in HBMSCs using remote magnetic particle mechano-activation

Nanomedicine. 2014 Jan;10(1):45-55. doi: 10.1016/j.nano.2013.06.014. Epub 2013 Jul 19.

Abstract

Physical cues have the potential to guide stem cell fate by coupling a mechanical stimulus to biochemical signaling. We have postulated that mechanical stimulation could provide a control method for cell therapy applications. This study investigates the use of functionalized magnetic nanoparticles to promote hBMSC differentiation towards a smooth muscle cell lineage by direct mechanical stimulation of platelet-derived growth factor receptor α and β (PDGFRα and β) via exposure to time-varying magnetic fields. Cyclical magneto-mechanical stimulation of PDGFR α over a 3h period results in up-regulation of smooth muscle α-actin expression in both protein and mRNA level. PDGFRα phosphorylation is detected in response to stimulation and the mRNA up-regulation is abrogated by pretreatment of cells with a receptor inhibitor, AG1296 or the neutralization antibody. Our results demonstrate proof of concept for remote controlled, locally-delivered mechanically induced differentiation of hBMSCs which could have applications in regenerative medicine.

From the clinical editor: Using a cyclical magneto-mechanical stimulator, this team of investigators demonstrated successful differentiation induction of human bone marrow-derived stem cells toward smooth muscle protein expression, with potential future applications in regenerative medicine.

Keywords: Biomechanics; Differentiation; Magnetic nanoparticle; Mesenchymal stem cell; Platelet-derived growth factor receptor; Smooth muscle α actin.

MeSH terms

  • Actins / biosynthesis
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects*
  • Cell Differentiation / drug effects*
  • Humans
  • Magnetite Nanoparticles / administration & dosage*
  • Magnetite Nanoparticles / chemistry
  • Mechanical Phenomena
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects
  • Phosphorylation / drug effects
  • RNA, Messenger / biosynthesis
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Regenerative Medicine
  • Tyrphostins / pharmacology

Substances

  • Actins
  • Magnetite Nanoparticles
  • RNA, Messenger
  • Tyrphostins
  • 6,7-dimethoxy-3-phenylquinoxaline
  • Receptor, Platelet-Derived Growth Factor alpha
  • Receptor, Platelet-Derived Growth Factor beta