Pharmacological tools to mobilise mesenchymal stromal cells into the blood promote bone formation after surgery

Fellous, Tariq G.; Redpath, Andia N.; Fleischer, Mackenzie M; Gandhi, Sapan D.; Hartner, Samantha; Newton, Michael D.; François, Moïra; Wong, Suet‐Ping; Gowers, Kate H.C.; Fahs, Adam M.; Possley, Daniel R.; Bron, Dominique; Urquhart, Paula; Nicolaou, Anna; Baker, Kevin C.; Rankin, Sara M.

doi:10.1038/s41536-020-0088-1

Cited by 7 publications

(3 citation statements)

References 47 publications

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“…CXCL12 has also been reported to promote early vascular formation when co-administered with MSC, which was equivalent to MSC co-administration of endothelial progenitor cells [114]. In contrast, the Food and Drug Administration (FDA) approved C-X-C chemokine receptor type 4 (CXCR4) antagonist, AMD3100, also activates MSC mobilization within the circulation, which assisted in femoral and spinal bone regeneration [115,116]. These observations suggest that CXCL12 can be utilized in multiple ways to help facilitate MSC mediated bone regeneration.…”

Section: Repair Of the Long Bones And Vertebraementioning

confidence: 99%

Clinical Application of Bone Marrow Mesenchymal Stem/Stromal Cells to Repair Skeletal Tissue

Arthur

Gronthos

2020

IJMS

173

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There has been an escalation in reports over the last decade examining the efficacy of bone marrow derived mesenchymal stem/stromal cells (BMSC) in bone tissue engineering and regenerative medicine-based applications. The multipotent differentiation potential, myelosupportive capacity, anti-inflammatory and immune-modulatory properties of BMSC underpins their versatile nature as therapeutic agents. This review addresses the current limitations and challenges of exogenous autologous and allogeneic BMSC based regenerative skeletal therapies in combination with bioactive molecules, cellular derivatives, genetic manipulation, biocompatible hydrogels, solid and composite scaffolds. The review highlights the current approaches and recent developments in utilizing endogenous BMSC activation or exogenous BMSC for the repair of long bone and vertebrae fractures due to osteoporosis or trauma. Current advances employing BMSC based therapies for bone regeneration of craniofacial defects is also discussed. Moreover, this review discusses the latest developments utilizing BMSC therapies in the preclinical and clinical settings, including the treatment of bone related diseases such as Osteogenesis Imperfecta.

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Section: Repair Of the Long Bones And Vertebraementioning

confidence: 99%

Clinical Application of Bone Marrow Mesenchymal Stem/Stromal Cells to Repair Skeletal Tissue

Arthur

Gronthos

2020

IJMS

173

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“…Moreover, therapeutic impact on motor function was only seen when applying a combination treatment with insulin-like growth factor 1. 54 Another strategy deserving further investigation is the pharmacological combination of AMD3100 with cobalt chloride or β3 adrenergic agonists in order to increase the mobilization of mesenchymal stromal cells from BM, 55,56 a cell population with a promising protective role in HIE. 1 Thus, it may be assumed that the subacute treatment with AMD3100 alone, despite clear evidence for therapeutic benefits in other forms of adult hypoxic-ischemic brain injury, may not be ideally suited for the treatment of HIE for so far unknown reasons.…”

Section: Discussionmentioning

confidence: 99%

Subacute AMD3100 Treatment Is Not Efficient in Neonatal Hypoxic-Ischemic Rats

Spiess

Campos

Conde

et al. 2022

Stroke

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Background and Purpose: Despite the advances in treating neonatal hypoxic-ischemic encephalopathy (HIE) with induced hypothermia, the rates of severe disability are still high among survivors. Preclinical studies have indicated that cell therapies with hematopoietic stem/progenitor cells could improve neurological outcomes in HIE. In this study, we investigated whether the administration of AMD3100, a CXCR4 antagonist that mobilizes hematopoietic stem/progenitor cells into the circulation, has therapeutic effects in HIE. Methods: P10 Wistar rats of both sexes were subjected to right common carotid artery occlusion or sham procedure, and then were exposed to hypoxia for 120 minutes. Two subcutaneous injections of AMD3100 or vehicle were given on the third and fourth day after HIE. We first assessed the interindividual variability in brain atrophy after experimental HIE and vehicle treatment in a small cohort of rats. Based on this exploratory analysis, we designed and conducted an experiment to test the efficacy of AMD3100. Brain atrophy on day 21 after HIE was defined as the primary end point. Secondary efficacy end points were cognitive (T-water maze) and motor function (rotarod) on days 17 and 18 after HIE, respectively. Results: AMD3100 did not decrease the brain atrophy in animals of either sex. Cognitive impairments were not observed in the T-water maze, but male hypoxic-ischemic animals exhibited motor coordination deficits on the rotarod, which were not improved by AMD3100. A separate analysis combining data from animals of both sexes also revealed no evidence of the effectiveness of AMD3100 treatment. Conclusions: These results indicate that the subacute treatment with AMD3100 does not improve structural and functional outcomes in a rat HIE model.

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“…Indeed, the expression of membrane markers such as CD29, CD44, CD73, and CD90, which all regulate MSC adhesion/migration processes, is known to change dramatically to allow MSC detachment and further migration ( Rege and Hagood, 2006 ; Ode et al, 2011 ; Qian et al, 2012 ; Xu and Li, 2014 ). Consequently, using flow cytometry analysis with a combination of surface markers (validated in vitro ) to detect circulating native MSCs may lead to underestimation and generates conflicting results when compared with studies using functional assays to detect MSCs [such as colony-forming unit-fibroblast (CFU-F) activity] ( Fellous et al, 2020 ; Figure 1 ). Indeed, the level of blood circulating CD45 – /CD271 + MSCs shows higher correlation to CFU-F numbers than the one of CD45 – /CD73 + /CD90 + /CD105 + MSCs ( Rebolj et al, 2018 ).…”

Section: What Do We Know About the Circulation Of Endogenous Mesenchymentioning

confidence: 99%

Endogenous Mobilization of Mesenchymal Stromal Cells: A Pathway for Interorgan Communication?

Girousse

Mathieu

Sastourné-Arrey

et al. 2021

Front. Cell Dev. Biol.

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To coordinate specialized organs, inter-tissue communication appeared during evolution. Consequently, individual organs communicate their states via a vast interorgan communication network (ICN) made up of peptides, proteins, and metabolites that act between organs to coordinate cellular processes under homeostasis and stress. However, the nature of the interorgan signaling could be even more complex and involve mobilization mechanisms of unconventional cells that are still poorly described. Mesenchymal stem/stromal cells (MSCs) virtually reside in all tissues, though the biggest reservoir discovered so far is adipose tissue where they are named adipose stromal cells (ASCs). MSCs are thought to participate in tissue maintenance and repair since the administration of exogenous MSCs is well known to exert beneficial effects under several pathological conditions. However, the role of endogenous MSCs is barely understood. Though largely debated, the presence of circulating endogenous MSCs has been reported in multiple pathophysiological conditions, but the significance of such cell circulation is not known and therapeutically untapped. In this review, we discuss current knowledge on the circulation of native MSCs, and we highlight recent findings describing MSCs as putative key components of the ICN.

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Pharmacological tools to mobilise mesenchymal stromal cells into the blood promote bone formation after surgery

Cited by 7 publications

References 47 publications

Clinical Application of Bone Marrow Mesenchymal Stem/Stromal Cells to Repair Skeletal Tissue

Clinical Application of Bone Marrow Mesenchymal Stem/Stromal Cells to Repair Skeletal Tissue

Subacute AMD3100 Treatment Is Not Efficient in Neonatal Hypoxic-Ischemic Rats

Endogenous Mobilization of Mesenchymal Stromal Cells: A Pathway for Interorgan Communication?

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