Stromal cell-derived factor-1 enhances distraction osteogenesis-mediated skeletal tissue regeneration through the recruitment of endothelial precursors

Fujio, Masahito; Yamamoto, Akihito; Ando, Yuji; Shohara, Ryutaro; Kinoshita, K; Kaneko, Tadashi; Hibi, Hideharu

doi:10.1016/j.bone.2011.06.024

Cited by 68 publications

(43 citation statements)

References 46 publications

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“…While the higher vasculogenic potential of UCB-derived ECFC is largely expected, the higher expression of osteogenesis-related genes here may reflect the intense skeletal development occurring during neonatal life as compared to the mature adult. These circulating ECFC are found at higher frequencies during neonatal life compared to adult life [46], with increased mobilization in the event of bony injury [47,48].…”

Section: Discussionmentioning

confidence: 99%

Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells

et al. 2012

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Umbilical cord blood‐derived endothelial colony‐forming cells (UCB‐ECFC) show utility in neovascularization, but their contribution to osteogenesis has not been defined. Cocultures of UCB‐ECFC with human fetal‐mesenchymal stem cells (hfMSC) resulted in earlier induction of alkaline phosphatase (ALP) (Day 7 vs. 10) and increased mineralization (1.9×; p < .001) compared to hfMSC monocultures. This effect was mediated through soluble factors in ECFC‐conditioned media, leading to 1.8–2.2× higher ALP levels and a 1.4–1.5× increase in calcium deposition (p < .01) in a dose‐dependent manner. Transcriptomic and protein array studies demonstrated high basal levels of osteogenic (BMPs and TGF‐βs) and angiogenic (VEGF and angiopoietins) regulators. Comparison of defined UCB and adult peripheral blood ECFC showed higher osteogenic and angiogenic gene expression in UCB‐ECFC. Subcutaneous implantation of UCB‐ECFC with hfMSC in immunodeficient mice resulted in the formation of chimeric human vessels, with a 2.2‐fold increase in host neovascularization compared to hfMSC‐only implants (p = .001). We conclude that this study shows that UCB‐ECFC have potential in therapeutic angiogenesis and osteogenic applications in conjunction with MSC. We speculate that UCB‐ECFC play an important role in skeletal and vascular development during perinatal development but less so in later life when expression of key osteogenesis and angiogenesis genes in ECFC is lower. Stem Cells2012;30:1911–1924

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Section: Discussionmentioning

confidence: 99%

Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells

et al. 2012

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“…72 In a murine model of high-speed distraction osteogenesis, where the bone fragments are distracted faster than normal, resulting in impaired callus formation, local injection of CXCL12 every other day rescued callus formation, increased the number of resident bone marrow endothelial and endothelial progenitor cells, and improved vascularization. 73 It is of note that CXCL12 has also been shown to induce the chemotactic recruitment of human osteoclast precursors, promote their differentiation into osteoclasts and regulate their activity and survival. 74,75 Osteoclast activity is essential for remodeling of woven bone in the hard callus, 76 although the interplay of CXCL12 and osteoclasts in the fracture environment has yet to be explored.…”

Section: Cxcl12 and Bone Regenerationmentioning

confidence: 99%

CXCL12/CXCR4 signaling and other recruitment and homing pathways in fracture repair

Yellowley¹

2013

BoneKEy Reports

119

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Cell recruitment, migration and homing to the fracture site are essential for the inflammatory process, neovascularization, chondrogenesis, osteogenesis and ultimately bone remodeling. Mesenchymal stem cells (MSCs) are required to navigate from local sources such as the periosteum and local bone marrow, and may also be recruited from the circulation and distant bone marrow. While the local recruitment process may involve matrix binding and degradation, systemic recruitment may utilize extravasation, a process used by leukocytes to exit the vasculature. CXCL12 (stromal cell-derived factor-1 (SDF-1)), a member of the CXC family of chemokines, is thought to have an important role in cell migration at the fracture site. However, there are many molecules upregulated in the hematoma and callus that have chemotactic potential not only for inflammatory cells but also for endothelial cells and MSCs. Surprisingly, there is little direct data to support their role in cell homing during bone healing. Current therapeutics for bone regeneration utilize local or systemic stem cell transplantation. More recently, a novel strategy that involves mobilization of large numbers of endogenous stem and progenitor cells from bone marrow into the circulation has been shown to have positive effects on bone healing. A more complete understanding of the molecular mechanisms underlying cell recruitment and homing subsequent to fracture will facilitate the fine-tuning of such strategies for bone.

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“…These include alpha-tocopherol (Kurklu et al, 2011); Adiponectin ; Inhibin A (Perrien et al, 2011); Nerve growth factor via a hydrogel (Cao et al, 2011); Thrombin peptide 508 (Cakarer et al, 2010); Bone marrow progenitor cell mobilizing agent (Davidson et al, 2011); Calcium sulphate injection (Song et al, 2004); Osteoblast-like cells (Shao et al, 2007); Stromal cell derived factor-1 (Fujio et al, 2011); NEL-like molecule-1 (Xue et al, 2011).…”

Section: Locally Applied Agentsmentioning

confidence: 99%

Distraction Osteogenesis and Its Challenges in Bone Regeneration

Hamdy¹,

Rendon²,

Tabrizian³

2012

Bone Regeneration

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Stromal cell-derived factor-1 enhances distraction osteogenesis-mediated skeletal tissue regeneration through the recruitment of endothelial precursors

Cited by 68 publications

References 46 publications

Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells

Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells

CXCL12/CXCR4 signaling and other recruitment and homing pathways in fracture repair

Distraction Osteogenesis and Its Challenges in Bone Regeneration

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