Role of SDF1/CXCR4 Interaction in Experimental Hemiplegic Models with Neural Cell Transplantation

Nagisa Arimitsu,Kenji Takai,Jun Shimizu,Naruyoshi Fujiwara,Noboru Suzuki,Tomoko Suzuki,Erika Takada,Takao Kono,Yuji Ueda

doi:10.3390/ijms13032636

Abstract

Much attention has been focused on neural cell transplantation because of its promising clinical applications. We have reported that embryonic stem (ES) cell derived neural stem/progenitor cell transplantation significantly improved motor functions in a hemiplegic mouse model. It is important to understand the molecular mechanisms governing neural regeneration of the damaged motor cortex after the transplantation. Recent investigations disclosed that chemokines participated in the regulation of migration and maturation of neural cell grafts. In this review, we summarize the involvement of inflammatory chemokines including stromal cell derived factor 1 (SDF1) in neural regeneration after ES cell derived neural stem/progenitor cell transplantation in mouse stroke models.

Highlights

Cerebral vascular diseases often cause severe neurological dysfunctions with high disability and mortality [1]
In the human physiological condition, several chemokines such as monocyte chemoattractant protein 1 (MCP1), cutaneous T cell-attracting chemokine (CTACK), stromal cell derived factor 1 (SDF1) and fractalkine are expressed on neural cells and astrocytes of the brain and on primary cells isolated from the CNS (Table 1)
We think that migration and subsequent maturation of the neural stem/progenitor cells transplanted to the damaged brain are mainly caused by SDF1 secreted from glial cells accumulating around the injured area (Figures 2 and 3b) [5]

Summary

Introduction

Cerebral vascular diseases often cause severe neurological dysfunctions with high disability and mortality [1]. The neural cells derived from the endogenous neural stem cells migrating from SVZ in the injured area occupy only 0.2% of the dead neurons in the middle cerebral artery occlusion (MCAO) model [13]. Continuous generation of neural cells is shown in both SVZ of the lateral ventricle and SGZ of the dentate gyrus in the mouse hippocampus; (c and d) Endogenous neural stem cell (NSC) migration to facilitate regeneration of the damaged area in the middle cerebral artery occlusion (MCAO) model. Numbers of the endogenous cells are insufficient to enable the repair of the damaged tissue; (e and f) Neural cell migration after ES cell derived NSC transplantation in the hemiplegic mouse with brain injury. We review chemokine regulation of neural regeneration after ES cell derived neural stem/progenitor cell transplantation

Chemokine Expressions in the CNS

Transplanted Neural Cells and Chemokines

Conclusions