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Stem Cells International
Volume 2017, Article ID 1478606, 17 pages
Research Article

From Blood to Lesioned Brain: An In Vitro Study on Migration Mechanisms of Human Nasal Olfactory Stem Cells

1Aix Marseille Univ, CNRS, NICN, Marseille, France
2VECT-HORUS SAS, Faculty of Medicine, Marseille, France
3Aix Marseille Univ, CNRS, CRN2M, Marseille, France
4Aix Marseille Univ, IFSTTAR, LBA, Marseille, France
5APHM, CHU Nord, ENT Department, Marseille, France
6APHM, Culture and Cell Therapy Laboratory, CIC BT 1409, Marseille, France

Correspondence should be addressed to François Féron; rf.uma-vinu@noref.siocnarf

Received 5 January 2017; Accepted 19 March 2017; Published 18 June 2017

Academic Editor: Christopher Dearth

Copyright © 2017 Stéphane D. Girard et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Stem cell-based therapies critically rely on selective cell migration toward pathological or injured areas. We previously demonstrated that human olfactory ectomesenchymal stem cells (OE-MSCs), derived from an adult olfactory lamina propria, migrate specifically toward an injured mouse hippocampus after transplantation in the cerebrospinal fluid and promote functional recoveries. However, the mechanisms controlling their recruitment and homing remain elusive. Using an in vitro model of blood-brain barrier (BBB) and secretome analysis, we observed that OE-MSCs produce numerous proteins allowing them to cross the endothelial wall. Then, pan-genomic DNA microarrays identified signaling molecules that lesioned mouse hippocampus overexpressed. Among the most upregulated cytokines, both recombinant SPP1/osteopontin and CCL2/MCP-1 stimulate OE-MSC migration whereas only CCL2 exerts a chemotactic effect. Additionally, OE-MSCs express SPP1 receptors but not the CCL2 cognate receptor, suggesting a CCR2-independent pathway through other CCR receptors. These results confirm that OE-MSCs can be attracted by chemotactic cytokines overexpressed in inflamed areas and demonstrate that CCL2 is an important factor that could promote OE-MSC engraftment, suggesting improvement for future clinical trials.