The effects of conditioned media generated by polarized macrophages on the cellular behaviours of bone marrow mesenchymal stem cells

Abstract

Macrophages (Mφs) are involved in a variety of physiological and pathological events including wound healing and tissue regeneration, in which they play both positive and negative roles depending on their polarization state. In this study, we investigated the cellular behaviours of bone marrow mesenchymal stem cells (BMMSCs) after incubation in different conditioned media (CMs) generated by unpolarized Mφs (M0) or polarized Mφs (M1 and M2). Mφ polarization was induced by stimulation with various cytokines, and CMs were obtained from in vitro Mφ cultures termed CM0, CM1 and CM2 based on each Mφ phenotype. We found that CM1 supported the proliferation and adipogenic differentiation of BMMSCs, whereas CM0 had a remarkable effect on cell osteogenic differentiation. To a certain degree, CM2 also facilitated BMMSC osteogenesis; in particular, cells incubated with CM2 exhibited an enhanced capacity to form robust stem cell sheets. Although incubation with CM1 also increased production of extracellular matrix components, such as fibronectin, COL-1 and integrin b1during sheet induction, the sheets generated by CM2-incubated cells were thicker than those generated by CM1-incubated cells (P < 0.001). Our data suggest that each Mφ phenotype has a unique effect on BMMSCs. Fine-tuning Mφ polarization following transplantation may serve as an effective method to modulate the therapeutic potential of BMMSCs.

M2 Macrophages Enhance the Cementoblastic Differentiation of Periodontal Ligament Stem Cells via the Akt and JNK Pathways

“…B, D, F). These data suggest that CM‐based investigations can be applied to explore the cell–cell interplay in an in vitro system . Although the positive effect of M2 Mφs on PDLSC cementoblastic differentiation has been demonstrated, PDLSCs incubated in CM‐M0 or cocultured with M0 Mφs (Trans‐M0) also expressed high levels of several cementoblastic differentiation‐related genes, such as CAP following CM‐based culture (Fig.…”

Macrophage populations show an M1‐to‐M2 transition in an experimental model of coronal pulp tissue engineering with mesenchymal stem cells

“…When macrophages are cocultured with MSCs in vitro, macrophage polarization can regulate MSC differentiation (Gong et al 2016). Furthermore, M1 macrophages exert various effects on proliferation, differentiation and matrix production of MSCs, and activated macrophage subpopulations would most likely enhance stem cell behaviours and facilitate tissue regeneration (He et al 2017). For example, TNF-a produced by M1 macrophages is proven to accelerate the differentiation of dental pulp cells to an odontoblastic phenotype (Paula-Silva et al 2009).…”

Platelet‐rich fibrin elicits an anti‐inflammatory response in macrophages in vitro

“…In vitro research on macrophage polarization involves murine marrow-derived macrophages and cell lines such as RAW 264.7, which are exposed to lipopolysaccharides (LPS) and IL4 to push the M1 and M2 phenotype, respectively. 19,20 Apart from LPS, M1 polarization is caused by saliva. 21 Among the main markers of M1 macrophages are the inflammatory cytokines IL1 and IL6.…”