Migratory mechanisms of MSCs. Figure 10 Inflammatory signals directing MSCs to the inflicted sites

Figure 10 Inflammatory signals directing MSCs to the inflicted sites. (Vinagolu and Rajasekhar., 2009)

Tissue damage recruits MSCs into the inflicted sites, where MSCs can participate in tissue regeneration and modulation of the immune response. Damaged tissues produce cytokines and chemokines, such as: transforming growth factor (TGF-β), interleukin-1 (IL-1), tumour necrosis factor (TNF-α) and stromal derived factor (SDF-1), which upregulate MSC chemotactic migration. (Figure 10) MSC migration through type I collagen-rich stromal tissues, is dependent on matrix metalloproteinase-2 (MMP-2), MMP-9 and membrane-type-1 matrix metalloproteinase (MTI-MMP), which degrade components of the extracellular matrix, allowing for stem cell motility and later differentiation. MMP-9 suppression reduced stem cells migration in the infarcted brain. Hepatocyte growth/scatter factor (HGF) is also produced by inflamed and damaged tissues, both human and mouse MSCs express a cognate receptor for HGF, c-Met.HGF induces MSC chemotaxis, yet inhibits proliferation.

Imitola et al., (2004) show that neural stem cells (NSCs) migrate in vivo toward an infarcted area, where surviving local astrocytes, microglia and endothelium up-regulate the inflammatory chemoattractants, including SDF-1α, which direct the migration of NSCs towards the penubmra. Both exogenous and endogenous NSCs express the cognate receptor for SDF-1α, CXCR4, which allows them to migrate towards the source of chemokines, home to the ischaemically damaged region and produce anti-inflammatory and anti-scarring molecules. (Figure 11)

Bhakta et al., (2006) state that most MSCs do not possess CXCR4, however, to optimize their migration and survival, CXCR4 gene can be expressed using retroviral transduction. In this study, MSCs were isolated from healthy volunteers, cultured and transduced with either a CXCR4 containing retroviral vector and green fluorescent protein (GFP) or only GFP - control vector. As expected, MSCs transduced with CXCR4 migrated significantly more toward SDF-1α. (Figure 12) Findings by Cheng et al., (2008) also support this statement.

Discussion

Conclusion

References

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