Abstract
Jaw periosteum-derived mesenchymal stem cells (JPCs) represent a promising cell source for bone tissue engineering in oral and maxillofacial surgery due to their high osteogenic potential and good accessibility. Our previous work demonstrated that JPCs are able to regulate THP-1-derived macrophage polarization in a direct coculture model. In the present study, we used an innovative horizontal coculture system in order to understand the underlying paracrine effects of JPCs on macrophage phenotype polarization. Therefore, JPCs and THP-1-derived M1/M2 macrophages were cocultured in parallel chambers under the same conditions. After five days of horizontal coculture, flow cytometric, gene and protein expression analyses revealed inhibitory effects on costimulatory and proinflammatory molecules/factors as well as activating effects on anti-inflammatory factors in M1 macrophages, originating from multiple cytokines/chemokines released by untreated and osteogenically induced JPCs. A flow cytometric assessment of DNA synthesis reflected significantly decreased numbers of proliferating M1/M2 cells when cocultured with JPCs. In this study, we demonstrated that untreated and osteogenically induced JPCs are able to switch macrophage polarization from a classical M1 to an alternative M2-specific phenotype by paracrine secretion, and by inhibition of THP-1-derived M1/M2 macrophage proliferation.
Highlights
The success of bone tissue engineering constructs depends on the immune reaction of the recipient’s body
In order to study the effects of Jaw periosteal cells (JPCs)/OBJPCs on THP-1-derived M1/M2 macrophages (M1/M2) polarization, the cell surface markers expression of M1 or M2 macrophages cocultured with or without JPCs/OBJPCs were measured by flow cytometry after 5 days of coculture
We examined the influence of JPCs on M1/M2 macrophage polarization when they were cocultured in direct contact and we showed
Summary
The success of bone tissue engineering constructs depends on the immune reaction of the recipient’s body. MSCs do maintain tissue homeostasis by supporting the functions of connective tissue cells, and by interacting with hematopoietic progenitors, but they regulate many types of innate immune cells, such as macrophages and dendritic cells at the microenvironmental site of inflammation [1,3,4,5]. Jaw periosteal cells (JPCs) show MSCs characteristics and have a high osteogenic potential and good accessibility. They are considered as a promising cell source for regenerative therapies in oral and maxillofacial surgery. Since JPCs are, like all other MSC types, multipotent, the desired differentiation lineage should be predefined before transplantation into the bone defect site. Our previous studies demonstrated that untreated and predifferentiated JPCs can partially inhibit dendritic cell maturation in a transwell coculture system and regulate macrophages differentiation in a direct contact coculture system [6,7]
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