Abstract
Homing of peripheral stem cells is regulated by one of the most representative homing factors, stromal cell-derived factor 1 alpha (SDF-1α), which specifically binds to the plasma membrane receptor CXCR4 of mesenchymal stem cells (MSCs) in order to initiate the signaling pathways that lead to directional migration and homing of stem cells. This complex homing process and directional migration of stem cells have been mimicked on a microfluidic device that is capable of generating a chemokine gradient within the collagen matrix and embedding endothelial cell (EC) monolayers to mimic blood vessels. On the microfluidic device, stem cells showed directional migration toward the higher concentration of SDF-1α, whereas treatment with the CXCR4 antagonist AMD3100 caused loss of directionality of stem cells. Furthermore, inhibition of stem cell’s main migratory signaling pathways, Rho-ROCK and Rac pathways, caused blockage of actomyosin and lamellipodia formation, decreasing the migration distance but maintaining directionality. Stem cell homing regulated by SDF-1α caused directional migration of stem cells, while the migratory ability was affected by the activation of migration-related signaling pathways.
Highlights
Stem cell homing is a controlled recruitment of stem cells within the vascular endothelium that leads to trans-endothelial and directional migration
We describe the directional migration of mesenchymal stem cells (MSCs) under a gradient of homing factors using a microfluidic channel
Stem cell homing is a crucial biological event that plays important roles in wound healing and tissue regeneration. This experiment showed the implementation of stem cell homing on a PDMS-based microfluidic device. This microfluidic device could provide different conditions such as a chemical gradient affecting the behavior of cells
Summary
Stem cell homing is a controlled recruitment of stem cells within the vascular endothelium that leads to trans-endothelial and directional migration. Liver, and other organs can be regenerated by stem cell homing through well-directed migration of stem cells. The directional migration of stem cell is precisely regulated by the homing factors released from the injury sites. The released soluble cytokines, homing factors, contribute to generating the cytokine gradient that determines the direction of stem cell migration. The bio-chemical gradient induces stem cells to migrate to the injury site for regeneration.
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