C-C Motif Chemokine Ligand 2 Enhances Macrophage Chemotaxis, Osteogenesis, and Angiogenesis during the Inflammatory Phase of Bone Regeneration.
Issei ShinoharaMasanori TsubosakaMasakazu ToyaMax L LeeJunichi KushiokaMasatoshi MurayamaQi GaoXueping LiNing ZhangSimon Kwoon-Ho ChowTomoyuki MatsumotoRyosuke KurodaStuart B GoodmanPublished in: Biomolecules (2023)
Local cell therapy has recently gained attention for the treatment of joint diseases and fractures. Mesenchymal stem cells (MSCs) are not only involved in osteogenesis and angiogenesis, but they also have immunomodulatory functions, such as inducing macrophage migration during bone regeneration via macrophage crosstalk. C-C motif chemokine ligand 2 (CCL2), a known inflammatory mediator, is associated with the migration of macrophages during inflammation. This study examined the utility of CCL2 as a therapeutic target for local cell therapy. Using lentiviral vectors for rabbit MSCs, genetically modified CCL2 overexpressing MSCs were generated. Osteogenic differentiation assays were performed using MSCs with or without macrophages in co-culture, and cell migration assays were also performed. Additionally, co-cultures were performed with endothelial cells (ECs), and angiogenesis was evaluated using a tube formation assay. Overexpression of CCL2 did not affect bone formation under monoculture conditions but promoted chemotaxis and osteogenesis when co-cultured with macrophages. Furthermore, CCL2 -overexpression promoted tube formation in co-culture with ECs. These results suggest that CCL2 induces macrophage chemotaxis and osteogenesis by promoting crosstalk between MSCs and macrophages; CCL2 also stimulates ECs to induce angiogenesis. These findings indicate that CCL2 may be a useful therapeutic target for local cell therapy in areas of bone loss.
Keyphrases
- cell therapy
- mesenchymal stem cells
- bone regeneration
- endothelial cells
- umbilical cord
- liver fibrosis
- liver injury
- bone marrow
- drug induced
- vascular endothelial growth factor
- stem cells
- oxidative stress
- high throughput
- cell migration
- adipose tissue
- bone loss
- transcription factor
- wound healing
- high glucose
- smoking cessation