Directional migration of mesenchymal stem cells under an SDF-1α gradient on a microfluidic device

• Published in: PloS one Vol. 12; no. 9; p. e0184595
• Main Authors: Park, Siwan, Jang, Hwanseok, Kim, Byung Soo, Hwang, Changmo, Jeong, Gi Seok, Park, Yongdoo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08-09-2017; Public Library of Science (PLoS)
• Subjects: Actomyosin; Amides - pharmacology; Aminoquinolines - pharmacology; Biology and Life Sciences; Biomedical engineering; Blockage; Blood vessels; Brain research; Cancer; Cell adhesion & migration; Cell migration; Cell Movement - drug effects; Chemokine CXCL12 - chemistry; Chemokines; Collagen; CXCR4 protein; Cytokines; Embedding; Endothelium; Engineering and Technology; Heterocyclic Compounds - pharmacology; Homing; Human Umbilical Vein Endothelial Cells; Humans; Immunohistochemistry; Kinases; Lab-On-A-Chip Devices; Lamellipodia; Leukocyte migration; Life sciences; Medical research; Medicine; Medicine and Health Sciences; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - drug effects; Mesenchyme; Microfluidics; Microscopy, Confocal; Monolayers; Pathways; Physiology; Proteins; Pseudopodia; Pyridines - pharmacology; Pyrimidines - pharmacology; rac GTP-Binding Proteins - antagonists & inhibitors; rac GTP-Binding Proteins - metabolism; rho GTP-Binding Proteins - antagonists & inhibitors; rho GTP-Binding Proteins - metabolism; Rodents; SDF-1 protein; Signal transduction; Signal Transduction - drug effects; Stem cells
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0184595

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.