Ccl2/Ccr2 signalling recruits a distinct fetal microchimeric population that rescues delayed maternal wound healing.
Mathieu CastelaDany NassarMaria SbeihMarie JachietZhe WangSelim AractingiPublished in: Nature communications (2017)
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.
Keyphrases
- birth weight
- wound healing
- pregnancy outcomes
- endothelial cells
- cell therapy
- induced apoptosis
- dendritic cells
- regulatory t cells
- liver injury
- liver fibrosis
- gestational age
- pregnant women
- stem cells
- cell cycle arrest
- weight gain
- drug induced
- mouse model
- type diabetes
- cell death
- mesenchymal stem cells
- bone marrow
- cell proliferation
- oxidative stress
- binding protein
- vascular endothelial growth factor