Long‐term administration of AMD3100, an antagonist of SDF‐1/CXCR4 signaling, alters fracture repair

Toupadakis, Chrisoula A.; Wong, Alice; Genetos, Damian C.; Chung, Dai-Jung; Murugesh, Deepa K.; Anderson, Matthew; Loots, Gabriela G.; Christiansen, Blaine A.; Kapatkin, Amy S.; Yellowley, Clare E.

doi:10.1002/jor.22145

Cited by 71 publications

(84 citation statements)

References 47 publications

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“…S4), which may mediate the migration of potentially regenerative stem cells into tissues (40). This result may be particularly important given that the inhibition of CXCL12 or corresponding C-X-C chemokine receptor type 4 was recently reported to delay bone fracture repair (41). Similarly, the parallel up-regulation of the C-X3-C chemokine motif ligand 1 observed after CCL22 microparticle treatment (Fig.…”

Section: Discussionmentioning

confidence: 77%

Prevention of inflammation-mediated bone loss in murine and canine periodontal disease via recruitment of regulatory lymphocytes

Glowacki

Yoshizawa

Jhunjhunwala

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

170

183

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Significance Periodontal disease (gum disease) is an extremely prevalent inflammatory disease initiated by persistent bacterial insult, leading to the destruction of bone and gingival tissues. Current clinical treatments focus solely on the removal of bacteria. In this study, we put forth a strategy to address the underlying inflammatory imbalance in periodontal disease by harnessing the body’s own sophisticated immunoregulatory mechanisms through the recruitment of regulatory T cells (Tregs). This is accomplished by controllably releasing small quantities (nanogram/kilogram range) of chemokine recognized by Tregs using biodegradable, resorbable polymers with an excellent track record of regulatory approval. Administration of Treg-recruiting treatments to the gingiva of mice and canines reduces clinical scores of disease as well as hard and soft tissue destruction.

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Section: Discussionmentioning

confidence: 77%

Prevention of inflammation-mediated bone loss in murine and canine periodontal disease via recruitment of regulatory lymphocytes

Glowacki

Yoshizawa

Jhunjhunwala

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

170

183

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“…59 In a murine model of fracture healing, we identified CXCL12 expression in the fracture callus in hypertrophic cartilage and immature cartilage close to pre-existing cortical bone. 66 Furthermore, CXCL12 staining colocalized with staining for Hypoxyprobe (pimonidazole hydrochloride; Hypoxyprobe, Inc., Burlington, MA, USA) a marker of hypoxic cells. 66 Almost all cells in the callus, including chondrocytes, osteoblasts, osteoclasts and undifferentiated mesenchymal Homing mechanisms in fracture repair C Yellowley tissue cells, stained positively for CXCR4.…”

Section: Cxcl12 and Bone Regenerationmentioning

confidence: 96%

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

Yellowley¹

2013

BoneKEy Reports

124

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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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“…Specific chemokine receptors (e.g., CCR1, CCR7, CCR9, CXCR4, CXCR5, and CXCR6) are important mediators in this matter, and among them CXCR4 and its ligand (CXCL12 or stromal-derived factor 1; SDF1) are the most widely investigated mediators in the MSC recruitment process [Kitaori et al, 2009]. A localized hypoxic condition occurs in the initial stage of fracture due to vascular damage that acts as a useful recruitment factor and regulatory stimulus for MSCs and other progenitor cells [Mehta et al, 2012;Toupadakis et al, 2012]. It has also been suggested that new bone formation occurs under hypoxic conditions [Olmsted-Davis et al, 2007].…”

Section: Msc Homing and Recruitment To Bone Defectsmentioning

confidence: 99%

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

Oryan

Kamali²,

Moshiri³

et al. 2017

Cells Tissues Organs

292

204

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Healing and regeneration of bone injuries, particularly those that are associated with large bone defects, are a complicated process. There is growing interest in the application of osteoinductive and osteogenic growth factors and mesenchymal stem cells (MSCs) in order to significantly improve bone repair and regeneration. MSCs are multipotent stromal stem cells that can be harvested from many different sources and differentiated into a variety of cell types, such as preosteogenic chondroblasts and osteoblasts. The effectiveness of MSC therapy is dependent on several factors, including the differentiating state of the MSCs at the time of application, the method of their delivery, the concentration of MSCs per injection, the vehicle used, and the nature and extent of injury, for example. Tissue engineering and regenerative medicine, together with genetic engineering and gene therapy, are advanced options that may have the potential to improve the outcome of cell therapy. Although several in vitro and in vivo investigations have suggested the potential roles of MSCs in bone repair and regeneration, the mechanism of MSC therapy in bone repair has not been fully elucidated, the efficacy of MSC therapy has not been strongly proven in clinical trials, and several controversies exist, making it difficult to draw conclusions from the results. In this review, we update the recent advances in the mechanisms of MSC action and the delivery approaches in bone regenerative medicine. We will also review the most recent clinical trials to find out how MSCs may be beneficial for treating bone defects.

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Long‐term administration of AMD3100, an antagonist of SDF‐1/CXCR4 signaling, alters fracture repair

Cited by 71 publications

References 47 publications

Prevention of inflammation-mediated bone loss in murine and canine periodontal disease via recruitment of regulatory lymphocytes

Prevention of inflammation-mediated bone loss in murine and canine periodontal disease via recruitment of regulatory lymphocytes

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

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

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