Migratory mechanisms of MSCs. Imitola et al., (2004) show that neural stem cells (NSCs) migrate in vivo toward an infarcted area, where surviving local astrocytes

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 10)

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 11) Findings by Cheng et al., (2008) also support this statement.

Matrix metalloproteinase-9 (MMP-9) is involved in the motility of stem cells by degrading components of the extracellular matrix. MMP-9 suppression reduced stem cells migration in the infarcted brain. Therefore, both stromal cell-derived factor-1α and MMP-9 expression appear to be essential for the homing ability of stem cells. (Tsai et al., 2011) The study has also found that priming MSCs with VPA or lithium increased homing to the cerebral infarcted regions via CXCR4 and MMP-9 upregulation, and copriming with VPA and lithium further enhanced this effect. MSC were labeled with BrdU before transplantation. Homing MSCs were detected using immunohistochemistry. (Figure 12)

Figure 12 Priming with VPA and/or lithium promotes MSC (green) homing into infarcted brain regions. In the ischemic frontal cortex (A) and striatum (B), the number of BrdU-positive cells increased when MSC were primed with sodium VPA and/or lithium chloride before transplantation. (Tsai et al., 2011)  

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