CCL2 promotes osteogenesis by facilitating macrophage migration during acute inflammation

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Orthopedics

Background:

• Complex fractures and bone defects in the elderly require novel minimally invasive treatments for robust bone healing.
• Local cell therapy using mesenchymal stromal cells (MSCs) is a potential strategy, leveraging their osteogenic and immunomodulatory roles.
• MSC-macrophage crosstalk is crucial for bone regeneration, with C-C motif chemokine ligand 2 (CCL2) influencing the migration of both cell types.

Purpose of the Study:

• To investigate the therapeutic potential of targeting C-C motif chemokine ligand 2 (CCL2) for local cell therapy in bone healing.
• To evaluate the effect of CCL2 on MSC osteogenic differentiation and MSC-macrophage interactions.
• To assess the role of CCL2-overexpressing MSCs in promoting bone regeneration.

Main Methods:

• MSCs and macrophages were isolated from BALB/c mice.
• Genetically modified MSCs overexpressing CCL2 were created using a lentivirus vector.
• Osteogenic differentiation and cell migration assays were performed in co-cultures of MSCs and macrophages with or without CCL2 stimulation.

Main Results:

• Genetically modified MSCs exhibited significantly higher CCL2 secretion without affecting cell proliferation.
• Acute CCL2 stimulation (1 day), but not sustained stimulation (7 days), significantly increased osteogenic differentiation in MSC-macrophage co-cultures.
• Both recombinant CCL2 and CCL2 secreted by MSCs effectively promoted macrophage migration.

Conclusions:

• Acute CCL2 stimulation enhances osteogenesis in MSC-macrophage co-cultures, suggesting a role in the early inflammatory phase of bone healing.
• CCL2 facilitates bone healing by directing macrophage migration, fostering MSC-macrophage crosstalk, and potentially licensing MSCs.
• Combining CCL2, MSCs, and macrophages presents a promising strategy for treating compromised bone healing.