Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 14, Issue 4, Pages 1149-1159Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2018.02.008
Keywords
Human adipose derived stem cells; Magnetic nanoparticles; Activin A receptor; TGF-beta/Smad2/3 signaling pathway; Tendon tissue engineering
Funding
- European Union Framework Programme for Research and Innovation HORIZON 2020, under the TEAMING Grant [739572]
- Norte Portugal Regional Operational Programme (NORTE 2020) through the European Regional Development Fund (ERDF)
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Stem cell therapies hold potential to stimulate tendon regeneration and homeostasis, which is maintained in response to the native mechanical environment. Activins are members of the mechano-responsive TGF-beta superfamily that participates in the regulation of several downstream biological processes. Mechanosensitive membrane receptors such as activin can be activated in different types of stem cells via magnetic nanoparticles (MNPs) through remote magnetic actuation resulting in cell differentiation. In this work, we target the Activin receptor type IIA (ActRIIA) in human adipose stem cells (hASCs), using anti-ActRIIA functionalized MNPs, externally activated through a oscillating magnetic bioreactor. Upon activation, the phosphorylation of Smad2/3 is induced allowing translocation of the complex to the nucleus, regulating tenogenic transcriptional responses. Our study demonstrates the potential remote activation of MNPs tagged hASCs to trigger the Activin receptor leading to tenogenic differentiation. These results may provide insights toward tendon regeneration therapies. (C) 2018 Elsevier Inc. All rights reserved.
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