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Clinical Orthopaedics and Related Research®

Published in:

01-09-2012 | Symposium: Allograft Research and Transplantation

Adult Stem Cell Mobilization Enhances Intramembranous Bone Regeneration: A Pilot Study

Authors: Margaret A. McNulty, PhD, Amarjit S. Virdi, PhD, Kent W. Christopherson, PhD, Kotaro Sena, DDS, PhD, Robin R. Frank, BS, Dale R. Sumner, PhD

Published in: Clinical Orthopaedics and Related Research® | Issue 9/2012

Abstract

Background

Stem cell mobilization, which is defined as the forced egress of stem cells from the bone marrow to the peripheral blood (PB) using chemokine receptor agonists, is an emerging concept for enhancing tissue regeneration. However, the effect of stem cell mobilization by a single injection of the C-X-C chemokine receptor type 4 (CXCR4) antagonist AMD3100 on intramembranous bone regeneration is unclear.

Questions/purposes

We therefore asked: Does AMD3100 mobilize adult stem cells in C57BL/6 mice? Are stem cells mobilized to the PB after marrow ablation? And does AMD3100 enhance bone regeneration?

Methods

Female C57BL/6 mice underwent femoral marrow ablation surgery alone (n = 25), systemic injection of AMD3100 alone (n = 15), or surgery plus AMD3100 (n = 57). We used colony-forming unit assays, flow cytometry, and micro-CT to investigate mobilization of mesenchymal stem cells, endothelial progenitor cells, and hematopoietic stem cells to the PB and bone regeneration.

Results

AMD3100 induced mobilization of stem cells to the PB, resulting in a 40-fold increase in mesenchymal stem cells. The marrow ablation injury mobilized all three cell types to the PB over time. Administration of AMD3100 led to a 60% increase in bone regeneration at Day 21.

Conclusions

A single injection of a CXCR4 antagonist lead to stem cell mobilization and enhanced bone volume in the mouse marrow ablation model of intramembranous bone regeneration.

Clinical Relevance

The emerging paradigm of mobilizing endogenous adult stem cells to stimulate tissue regeneration may lead to novel therapeutic strategies for improving repair of skeletal tissues.

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Title: Adult Stem Cell Mobilization Enhances Intramembranous Bone Regeneration: A Pilot Study
Authors: Margaret A. McNulty, PhD
Amarjit S. Virdi, PhD
Kent W. Christopherson, PhD
Kotaro Sena, DDS, PhD
Robin R. Frank, BS
Dale R. Sumner, PhD
Publication date: 01-09-2012
Publisher: Springer-Verlag
Published in: Clinical Orthopaedics and Related Research® / Issue 9/2012
Print ISSN: 0009-921X
Electronic ISSN: 1528-1132
DOI: https://doi.org/10.1007/s11999-012-2357-9

At a glance: The STEP trials

Springer Medicine

Adult Stem Cell Mobilization Enhances Intramembranous Bone Regeneration: A Pilot Study

Abstract

Background

Questions/purposes

Methods

Results

Conclusions

Clinical Relevance

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Questions/purposes

Methods

Results

Conclusions

Clinical Relevance

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