4th Annual Mountain West
Biomedical Engineering Conference

Multi-nucleated giant cells are associated with foreign implanted materials (foreign body giant cells, FBGCs) or within mycobacterium-induced granulomas (Langhans’ giant cells). Giant cells are also found in non-pathological roles such as osteoclasts – multi-nucleated cells responsible for bone resorption. Many FBGCs appear to be multi-cell fusion products of macrophage origin, yet it is unknown how many other cell types may possess this fusogenic phenotype involved in FBGCs relevant to implanted materials. We report unusual fibroblastic fusions in various cultures that form multi-nucleated cells with characteristics similar to FBGCs. As the most prevalent cell type in tissue, fibroblasts are a primary effector of foreign body responses, contributing to fibrous encapsulation commonly observed around implanted biomaterials. We now show that fibroblasts fuse in vitro to form multi-nucleated cells both during contact co-culture with macrophages, without added exogenous cytokines (e.g., no IL-4, IL-13, GM-CSF) and after extended periods of serum-based mono-culture. Secondary transformed NIH 3T3 fibroblasts will rapidly fuse after 24 hours in contact with RAW 264.7 immortalized macrophages, while macrophage cultures alone and non-contact (transwell) co-cultures will not fuse within this same time frame. Primary-derived murine fibroblasts also form multi-nucleated cells, both in the presence or absence of co-cultured macrophages, and will increase their multi-nucleation during long-term culture (5-30 days). Furthermore, secondary (cell line) fibroblasts become multi-nucleated in the absence of macrophages at high passage numbers (>20). Understanding the mechanisms for this newly identified fibroblast fusogenic behavior, and the significance of the resulting giant cell is critical to defining their role in host tissue during normal and pathological responses, particularly since fusion has been primarily attributed to macrophages in this context. Determining the distinctions and similarities of these new fused cell types from more traditional macrophage-derived FBGCs, and their implications to the foreign body response and fibrotic capsule formation will be important in current and future work.