Triggering the activation of Activin A type II receptor in human adipose stem cells towards tenogenic commitment using mechanomagnetic stimulation

Research output: Contribution to journalArticlepeer-review

Authors

  • A. I. Gonçalves
  • M. Rotherham
  • H. Markides
  • M. T. Rodrigues
  • R. L. Reis
  • M. E. Gomes

Colleges, School and Institutes

External organisations

  • University of Minho

Abstract

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-β 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.

Details

Original languageEnglish
Pages (from-to)1149-1159
Number of pages11
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number4
Early online date20 Feb 2018
Publication statusPublished - 1 Jun 2018

Keywords

  • Activin A receptor, Human adipose derived stem cells, Magnetic nanoparticles, Tendon tissue engineering, TGF-β/Smad2/3 signaling pathway