Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 14, Issue 1, Pages 173-184Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2017.09.008
Keywords
Mesenchymal stem cells; Magnetic nanoparticles; Wnt signaling; Bone tissue engineering
Funding
- BBSRC [BB/G010579/1]
- European Union's Horizon research and innovation programme [686841]
- MRC [MR/P020941/1] Funding Source: UKRI
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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, beta-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. (C) 2017 Elsevier Inc. All rights reserved.
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