Endothelial Cells Enhance the Migration of Bovine Meniscus Cells

Objective. To study the interactions between vascular endothelial cells and meniscal fibrochondrocytes from the inner avascular and outer vascular regions of the meniscus and to identify angiogenic factors that enhance cell migration and integrative repair. Methods. Bovine meniscal fibrochondrocytes (bMFCs) from the inner and outer regions of meniscus were cultured for 7 days with or without human umbilical vein endothelial cells (HUVECs) in a micropatterned 3-dimensional hydrogel system for assessment of cell migration. Angiogenic factors secreted by HUVECs were probed for their role in paracrine mechanisms governing bMFC migration and applied to a full-thickness defect model of meniscal repair in explants from the inner and outer meniscal regions over 4 weeks. Results. Endothelial cells enhanced the migration of inner and outer bMFCs in the micropatterned system via endothelin 1 (ET-1) signaling. Supplementation with ET-1 significantly enhanced the integration strength of full-thickness defects in the inner and outer explants, as well as cell migration at the macroscale level, as compared to controls without ET-1 treatment. Conclusion. This study is the first to show that bMFCs from both the avascular and vascular regions of the meniscus respond to the presence of endothelial cells with increased migration. Paracrine signaling by endothelial cells regulates the bMFCs differentially by region, but we identified ET-1 as an angiogenic factor that stimulates the migration of inner and outer cells at the microscale level and the integrative repair of inner and outer explants at the macroscale level. These findings reveal the regional interactions between the vasculature and MFCs, and suggest ET-1 as a potential new treatment for avascular meniscus injuries in order to prevent the development of osteoarthritis.