Title:The SDF-1/CXCR4 Signaling Pathway Directs the Migration of Systemically
Transplanted Bone Marrow Mesenchymal Stem Cells Towards the
Lesion Site in a Rat Model of Spinal Cord Injury
Volume: 18
Issue: 2
Author(s): Andong Zhao, Manhon Chung, Yi Yang, Xiaohua Pan, Yu Pan*Sa Cai*
Affiliation:
- Department of Trauma and Orthopedics, The 2nd Affiliated Hospital of Shenzhen University, Health Science Center,
Shenzhen University, Shenzhen, China
- Department of Trauma and Orthopedics, The 2nd Affiliated Hospital of Shenzhen University, Health Science Center,
Shenzhen University, Shenzhen, China
Keywords:
Bone marrow mesenchymal stem cells, spinal cord injury, migration, SDF-1, CXCR4, neural regeneration.
Abstract:
Background: It has been observed that bone marrow-derived mesenchymal stem cells (MSCs)
migrate towards the injured spinal cord and promote functional recovery when systemically transplanted
into the traumatized spinal cord. However, the mechanisms underlying their migration to the spinal cord
remain poorly understood.
Methods: In this study, we systemically transplanted GFP- and luciferase-expressing MSCs into rat models
of spinal cord injury and examined the role of the stromal cell-derived factor 1 (SDF-1)/CXCR4 axis
in regulating the migration of transplanted MSCs to the spinal cord. After intravenous injection, MSCs
migrated to the injured spinal cord where the expression of SDF-1 was increased. Spinal cord recruitment
of MSCs was blocked by pre-incubation with an inhibitor of CXCR4. Their presence correlated with
morphological and functional recovery. In vitro, SDF-1 or cerebrospinal fluid (CSF) collected from SCI
rats promoted a dose-dependent migration of MSCs in culture, which was blocked by an inhibitor of
CXCR4 or SDF-1 antibody.
Results and Conclusion: The study suggests that SDF-1/CXCR4 interactions recruit exogenous MSCs to
injured spinal cord tissues and may enhance neural regeneration. Modulation of the homing capacity may
be instrumental in harnessing the therapeutic potential of MSCs.