Abstract

White matter tracts are important for the trafficking of neural progenitor cells (NPCs) in both normal and pathological conditions, but the underlying mechanism is not clear. The directionality of white matter is advantageous for molecules or cells to distribute over a long distance, but this feature is unlikely solely responsible for efficient migration. The present study hypothesizes that the efficient migration of NPCs into white matter is under the influences of neurochemical attraction—CXCL12/CXCR4 signaling, a major mechanism underlying the targeted migration of NPCs. To test this view, the present study investigated the effects of CXCL12 administration into the corpus callosum (CC) on the migratory behavior of transplanted NPCs. A living animal tracking platform based on MRI and a magnetic cell labeling technique was employed. The NPCs were magnetically labeled and then transplanted at the right end of the CC. CXCL12 was infused continuously at the left end. Migration of NPCs was monitored repeatedly over a 7-day course using 3D gradient echo T2*-weighted imaging. It was found that, CXCL12 induced NPCs to migrate up to 1,881 μm from the graft whereas the spontaneous migration was mere 200 μm. CXCL12 induced migration that was nine times as efficient in the speed. The results indicate that the CXCL12/CXCR4 signaling may be a mechanism via which NPCs efficiently migrate along the white matter tracts. The study also presents a potential strategy for facilitating the targeted migration in NPC therapy for brain disorders.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-014-0770-4) contains supplementary material, which is available to authorized users.

Highlights

  • White matter tracts, which mainly involve transmitting neural signals from one brain region to another, are important for the trafficking of neural progenitor cells (NPCs) (Suzuki and Goldman 2003; Yang et al 2009).Brain Struct Funct (2015) 220:2073–2085Both endogenous and transplanted NPCs exhibit the tendency to take advantage of the white matter tracts for migration regardless of the condition being normal or pathological

  • The present study hypothesizes that the efficient migration of NPCs into white matter is under the influences of neurochemical attraction—CXCL12/CXCR4 signaling, a major mechanism underlying the targeted migration of NPCs

  • The present study investigated whether neurochemical attraction via CXCL12/CXCR4 signaling is responsible for the efficient migration along the corpus callosum (CC)

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Summary

Introduction

Both endogenous and transplanted NPCs exhibit the tendency to take advantage of the white matter tracts for migration regardless of the condition being normal or pathological. The migration speed of engrafted NPCs through the CC was estimated to be 50–70 lm/day in the normal condition (Flexman et al 2011). Such spontaneous migration is relatively slow, suggesting the directional diffusion is unlikely solely responsible for the faster migration reported in many of the related studies (Kim et al 2004; Yang et al 2009; Zhang et al 2001)

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