CXCR4 Antagonism to Treat Delayed Fracture Healing

Meeson, R L and Sanghani, A and Coathup, M and Blunn, G (2019) CXCR4 Antagonism to Treat Delayed Fracture Healing. Tissue Engineering Part A, 25 (17-18). (In Press)

[img]
Preview
Text
11883.pdf - Accepted Version
Available under License Creative Commons Attribution Non-commercial.

Download (1MB) | Preview
[img]
Preview
Text
11883.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial.

Download (8MB) | Preview

Abstract

A significant number of fractures develop non-union. Stem cell homing is regulated through SDF-1 and its receptor CXCR4. Stem/progenitor cell populations can be endogenously mobilised by administering growth factors with a pharmacological antagonist of CXCR4, AMD3100, which may be a means to improve fracture healing. Methods: A 1.5mm femoral osteotomy in Wistar rats was stabilised with an external fixator. Rats were pre-treated with PBS(P), VEGF(V), IGF-1(I) or GCSF(G) prior to AMD3100. A control group (C) did not receive growth factors or AMD3100. Bone formation after five weeks was analysed. Results: Group P had a significant increase in total bone volume (p=0.01) and group I in % bone in the fracture gap (p=0.035). Group G showed a decrease in bone volume. All treated groups had an increase in trabecular thickness. Histology showed decreased cartilage tissue associated with increased bone in groups with improved healing, and increased fibrous tissue in poorly performing groups. Conclusion: Antagonism of SDF1-CXCR4 axis can boost impaired fracture healing. AMD3100 given alone was the most effective means to boost healing whilst pre-treatment with GCSF reduced healing. AMD3100 is likely mobilizing stem cells into the blood stream that home to the fracture site enhancing healing.

Actions (Repository Editors)

View Item View Item