title: Control of smooth muscle α-actin (SMA) up-regulation in HBMSCs using remote magnetic particle mechano-activation.
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.
  
  
  BACKGROUND
  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.
authors.affiliation: Institute of Science and Technology in Medicine, Keele University, UK.
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.affiliation: Institute of Science and Technology in Medicine, Keele University, UK; J. Crayton Puritt Family Department of Biomedical Engineering, Department of Materials Science and Engineering, Institute for Cell Engineering and Regenerative Medicine (ICERM), University of Florida, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Dobson
authors.affiliation: Institute of Science and Technology in Medicine, Keele University, UK. Electronic address: a.j.el.haj@keele.ac.uk.
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: El Haj
mesh_terms: D000199:Actins / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D006801:Humans; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D055595:Mechanical Phenomena; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D044968:Regenerative Medicine; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D000199:Actins; D058185:Magnetite Nanoparticles; D012333:RNA, Messenger; D020032:Tyrphostins; C106250:6,7-dimethoxy-3-phenylquinoxaline; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: Biomechanics; Differentiation; Magnetic nanoparticle; Mesenchymal stem cell; Platelet-derived growth factor receptor; Smooth muscle α actin