Remote regulation of magnetic particle targeted Wnt signaling for bone tissue engineering

Michael Rotherham, James R. Henstock, Omar Qutachi, Alicia J. El Haj

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)
112 Downloads (Pure)

Abstract

Wnt signaling is critically involved in the differentiation of human Mesenchymal Stem Cells (hMSC). Wnt proteins therefore have considerable therapeutic value, but are expensive and difficult to produce. UM206 is a synthetic peptide and ligand for the Wnt receptor Frizzled. Attachment of UM206 to magnetic nanoparticles (MNP) enables the ligand-MNP complex to be manipulated using magnetic fields, allowing control of Frizzled stimulation. Using this approach, Wnt signaling was activated in hMSC which resulted in Frizzled clustering, β-catenin translocalization and activation of TCF/LEF responsive transcription. During osteogenesis, UM206-MNP initiated localized mineralized matrix formation. Injection and magnetic stimulation of UM206-MNP-labeled MSC in ex vivo chick femurs resulted in increased mineralization which acted synergistically with addition of bone morphogenic protein 2 (BMP2) releasing micro-particles. As this facilitates external control over signal transduction, conjugated MNP technology has applications both as a research tool and for regulating tissue formation in clinical cell therapies.

Original languageEnglish
Pages (from-to)173-184
Number of pages12
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number1
Early online date29 Sep 2017
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Bone tissue engineering
  • Magnetic nanoparticles
  • Mesenchymal stem cells
  • Wnt signaling

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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