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Published on: May 19, 2016
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.
Abstract:
This study was designed to investigate the migratory behavior of adult human mesenchymal stem cells (MSC) and the underlying mechanism. Cell migration was assessed by transwell, wound healing and time-lapse in vivo motility assays. Pharmacological inhibitors were used to determine the potential mechanism responsible for cell migration and invasion. The tests that were implemented revealed that MSC were fairly migratory. Protein kinase B (AKT) was strongly activated at the basal level. Through our analyses we demonstrated that pharmacological inactivation of AKT2 but not AKT1 significantly decreased cell migration and invasion. Although preliminary, collectively our results indicate that AKT2 activation plays a critical role in enabling MSC migration.
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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