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

Stephane Girard (1) , Isabelle Virard (1) , Emmanuelle Lacassagne (1) , Jean-Michel Paumier (2) , Hanae Lahlou (3) , Françoise Jabès (4) , Yves Molino (4) , Delphine Stephan (1) , Kévin Baranger (2) , Maya Belghazi (5) , Arnaud Deveze (6) , Michel Khrestchatisky (1) , Emmanuel Nivet (2) , François S. Roman (3) , François Feron (2)

1 NICN - Neurobiologie des interactions cellulaires et neurophysiopathologie - NICN
2 NICN - Neurobiologie des interactions cellulaires et neurophysiopathologie - NICN
3 LNIA - Laboratoire de Neurosciences intégratives et adaptatives
4 Vect-Horus
5 CRN2M - Centre de recherche en neurobiologie - neurophysiologie de Marseille
6 LBA UMR T24 - Laboratoire de Biomécanique Appliquée

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.

Domains: Life Sciences [q-bio]; Neurons and Cognition [q-bio.NC]; Life Sciences [q-bio]; Neurons and Cognition [q-bio.NC]; Neurobiology; Cognitive science; Neuroscience

Stephane Girard, Isabelle Virard, Emmanuelle Lacassagne, Jean-Michel Paumier, Hanae Lahlou, et al.. From Blood to Lesioned Brain: An In Vitro Study on Migration Mechanisms of Human Nasal Olfactory Stem Cells. Stem Cells International, 2017, 2017, 1478606 (17 p.). ⟨10.1155/2017/1478606⟩. ⟨hal-02282115⟩