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

Date

2017-09-29

Advisors

Journal Title

Journal ISSN

ISSN

Volume Title

Publisher

Elsevier

Type

Article

Peer reviewed

Yes

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.

Description

The author's final peer reviewed version can be found by following the URI link. The Publisher's final version can be found by following the DOI link.

Keywords

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

Citation

Rotherham, M., Henstock, J.R., Qutachi, O., El-Haj, A.J. (2017) Remote regulation of magnetic particle targeted Wnt signaling for bone tissue engineering. Nanomedicine-Nanotechnology Biology And Medicine, 14 (1), pp. 173 - 184.

Rights

Research Institute