Ccl2/Ccr2 signalling recruits a distinct fetal microchimeric population that rescues delayed maternal wound healing
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Nature Publishing Group
Abstract
Foetal microchimeric cells (FMCs) traffic into maternal circulation during pregnancy and persist for decades after delivery. Upon maternal injury, FMCs migrate to affected sites where they participate in tissue healing. However, the specific signals regulating the trafficking of FMCs to injury sites had to be identified. Here we report that, in mice, a subset of FMCs implicated in tissue repair displays CD11b+ CD34+ CD31+ phenotype and highly express C-C chemokine receptor 2 (Ccr2). The Ccr2 ligand chemokine ligand 2 (Ccl2) enhances the recruitment of FMCs to maternal wounds where these cells transdifferentiate into endothelial cells and stimulate angiogenesis through Cxcl1 secretion. Ccl2 administration improves delayed maternal wound healing in pregnant and postpartum mice but never in virgin ones. This role of Ccl2/Ccr2 signalling opens new strategies for tissue repair through natural stem cell therapy, a concept that can be later applied to other types of maternal diseases. © The Author(s) 2017.
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Animals, Antigens, cd34, Cd11b antigen, Chemokine ccl2, Chemokine cxcl1, Endothelial progenitor cells, Female, Fetus, Gene expression regulation, Mice, Neovascularization, physiologic, Placental circulation, Platelet endothelial cell adhesion molecule-1, Pregnancy, Receptors, ccr2, Signal transduction, Wound healing, Wounds, nonpenetrating, Mus, Chemokine receptor ccr2, Enhanced green fluorescent protein, Monocyte chemotactic protein 1, Ccl2 protein, mouse, Ccr2 protein, mouse, Cd34 antigen, Cxcl1 chemokine, Cxcl1 protein, mouse, Pecam1 protein, mouse, Platelet endothelial cell adhesion molecule 1, Aging, Cells and cell components, Chemoreception, Ligand, Maternal health, Phenotype, Rodent, Wounding, Adult, Angiogenesis, Animal cell, Animal tissue, Article, Cell proliferation, Cell transdifferentiation, Controlled study, Cytokine release, Endothelium cell, Fetus cell, Fluorescence activated cell sorting, Gene expression, Immunofluorescence, Male, Maternal disease, Microchimerism, Monocyte, Mouse, Nonhuman, Rna sequence, Skin injury, Tissue repair, Wound healing impairment, Wound tissue, Animal, Blunt trauma, Cytology, Drug effect, Endothelial progenitor cell, Genetics, Metabolism, Pathology, Physiology, Placenta circulation