Speaker
Description
Macrophages are known as the most dominating cells at the wound site, and they coordinate the transition between tissue repair phases during the entire wound-healing process. Especially, anti-inflammatory macrophage (M2) subtypes, namely M2a and M2c, are reported to modulate the tissue repair process tightly and chronologically by modulating fibroblast differentiation state and functions. To establish a well-defined three-dimensional (3D) cell culture model to mimic the tissue repair process, we utilized THP-1 human monocytic cells and a 3D collagen matrix as a biomimetic tissue model. THP-1 cells were differentiated into macrophages and activated using IL-4/IL-13 (MIL-4/IL-13) and IL-10 (MIL-10). Both activated macrophages were characterized by both their cell surface marker expression and cytokine secretion profile. Our results demonstrated that surface markers and cytokines secretion profile of MIL-4/IL-13 and MIL-10 is akin to M2a and M2c macrophages derived from human PBMC, respectively. To mimic the initial and resolution phases during the tissue repair, both activated macrophages were co-cultured with fibroblasts and myofibroblasts. We showed that MIL-4/IL-13 can modulate tissue repair by controlled secretion of TGF-β1 to induce fibroblast differentiation, while MIL-10 macrophages secrete high amounts of IL-10 to resolve inflammation and tissue repair processes. Besides, we demonstrate that IL-10 can reverse myofibroblast into fibroblast phenotypes. By neutralizing IL-10 with antibody in co-culture with MIL-10, no dedifferentiation of myofibroblast could be observed, emphasizing the role of IL-10 in resolution of the tissue repair phase. Overall, our results pinpoint the importance of the co-culture model of fibroblast and macrophages for biomimetic wound healing, instead of fibroblast monoculture. In addition, our established biomimetic model can guide the development of well-defined high-throughput platforms for improving tissue healing and anti-fibrotic drugs testing, as well as other biomedical studies.
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