Protein kinase B/AKT isoform 2 drives migration of human mesenchymal stem cells

Zrinka Bulj1, Serena Duchi, Alessandro Bevilacqua

  • 1Department of Biomedical Sciences, Cellular Signalling Laboratory, Bologna, Italy.

Insights

Adult human mesenchymal stem cells (MSC) are migratory. AKT2 activation, a key signaling pathway, significantly enhances MSC migration and invasion, indicating its critical role.

Area of Science:

  • Cell Biology
  • Stem Cell Research
  • Molecular Biology

Background:

  • Mesenchymal stem cells (MSC) are known for their therapeutic potential.
  • Understanding MSC migratory behavior is crucial for regenerative medicine applications.
  • The molecular mechanisms regulating MSC migration require further elucidation.

Purpose of the Study:

  • To investigate the migratory behavior of adult human mesenchymal stem cells (MSC).
  • To identify the underlying molecular mechanisms, specifically focusing on Protein Kinase B (AKT) signaling.
  • To determine the role of AKT isoforms (AKT1 and AKT2) in MSC migration and invasion.

Main Methods:

  • Cell migration was assessed using transwell, wound healing, and time-lapse in vivo motility assays.
  • Pharmacological inhibitors targeting AKT signaling pathways were employed.
  • Comparative analysis of AKT1 and AKT2 inhibition on MSC migration was performed.

Main Results:

  • Adult human MSC demonstrated significant migratory capacity in vitro and in vivo.
  • Protein Kinase B (AKT) signaling was found to be constitutively active in MSC.
  • Pharmacological inactivation of AKT2, but not AKT1, markedly reduced MSC migration and invasion.

Conclusions:

  • AKT2 activation is a critical determinant of mesenchymal stem cell migration.
  • Targeting AKT2 may offer a strategy to modulate MSC behavior for therapeutic purposes.
  • These findings provide novel insights into the molecular regulation of MSC motility.

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