Systemic Administration of G-CSF Accelerates Bone Regeneration and Modulates Mobilization of Progenitor Cells in a Rat Model of Distraction Osteogenesis.

Flavy Roseren,Benjamin Guillet,Stéphane Robert,Martine Pithioux,Laure Balasse,Edouard Lamy,Sandrine Roffino

doi:10.3390/ijms22073505

Abstract

Granulocyte colony-stimulating factor (G-CSF) was shown to promote bone regeneration and mobilization of vascular and osteogenic progenitor cells. In this study, we investigated the effects of a systemic low dose of G-CSF on both bone consolidation and mobilization of hematopoietic stem/progenitor cells (HSPCs), endothelial progenitor cells (EPCs) and mesenchymal stromal cells (MSCs) in a rat model of distraction osteogenesis (DO). Neovascularization and mineralization were longitudinally monitored using positron emission tomography and planar scintigraphy. Histological analysis was performed and the number of circulating HSPCs, EPCs and MSCs was studied by flow cytometry. Contrary to control group, in the early phase of consolidation, a bony bridge with lower osteoclast activity and a trend of an increase in osteoblast activity were observed in the distracted callus in the G-CSF group, whereas, at the late phase of consolidation, a significantly lower neovascularization was observed. While no difference was observed in the number of circulating EPCs between control and G-CSF groups, the number of MSCs was significantly lower at the end of the latency phase and that of HSPCs was significantly higher 4 days after the bone lengthening. Our results indicate that G-CSF accelerates bone regeneration and modulates mobilization of progenitor cells during DO.

Highlights

As it has been shown that low doses of Granulocyte colony-stimulating factor (G-CSF) can mobilize mesenchymal stromal cells (MSCs) [58,59], we studied the mobilization of these cells
Since the participation of bone marrow-mobilized endothelial progenitor cells (EPCs) in neovascularization of injured tissue was clearly demonstrated [20], we investigated the formation of new blood vessels in the distracted callus during distraction osteogenesis (DO)
It did not provide data to characterize a beneficial effect of G-CSF on the mechanical behavior of the distracted callus

Summary

Introduction

DO is organized in three temporal phases: latency, active distraction, and consolidation. The latency period starts right after the osteotomy and ends before activation of the external device. During this phase, an inflammatory reaction occurs and contributes to the development of the callus. The consolidation phase ends when ceasing the distraction forces and mineralization of the distracted callus occurs, leading to an osseous union of the distracted gap [2]. In spite of its efficiency, DO can lead to numerus complications such as pseudarthrosis, infection, non-union and fractures [3,4,5,6]. Accelerating the bone regeneration is currently a challenge that would reduce the occurrence of these complications

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Discussion

Conclusion