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| Author | Cell source | Study type | Cell management | Involvement of Mφ polarization in MSC osteogenic induction | Proposed mechanisms |
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| Tu B 2015 | Human—BMSCs; THP-1—Mφs | In vitro | Mφ CM collected for treating BMSCs under osteogenic induction conditions | IL-23 secretion from proinflammatory Mφs promotes the osteogenesis of BMSCs | Mφ-secreted IL-23 activates the STAT3 and β-catenin signaling and thus promotes the osteogenic differentiation of BMSCs |
| Hirata E 2016 | Human—BMSCs; human—Mφs | In vitro | Coculture of BMSCs and Mφs in the presence of CNHs | ALP activity is increased under the coculture of Mφs and MSCs in the presence of CNHs | OSM from activated Mφs induces osteoblast differentiation and matrix mineralization through STAT3 |
| Shi M 2016 | Human—BMSCs; RAW 264.7—Mφs | In vitro | BMSCs cultured in Cu-MSN/Mφ CM under osteogenic differentiation | Mφs phagocytize Cu-MSNs and produce proinflammatory cytokines leading to better osteogenic differentiation of BMSCs | Cu-MSN/Mφ CM enhances the osteogenic differentiation of BMSCs through the activation of the OSM pathway |
| Lu LY 2017 | C57BL/6 mice—BMSCs; C57BL/6 mice—Mφs | In vitro | Coculture of BMSCs and polarized Mφs (M1 induced by LPS and M2 induced by IL-4) | Polarized Mφs enhance bone mineralization, especially proinflammatory M1 Mφs | M1 Mφs enhance BMSC osteogenesis and bone formation via the COX2-PGE2 pathway |
| Tang H 2017 | Human—ADSCs; THP-1—Mφs | In vitro | 3D spheroid cocultures of M1 Mφs and ADSCs are conducted under osteogenic differentiation conditions | The osteogenic differentiation of ADSCs is inhibited by M1 Mφs | N-cadherin-mediated cell-cell interactions between M1 Mφs and ADMSCs result in inhibited osteogenesis |
| Xue D 2018 | Human—BMSCs; RAW 264.7—Mφs | In vitro | BMSCs undergo osteogenic differentiation added with the CM from GO/Mφs | Coculture of GO and Mφs induced M1 Mφ transition and produced proinflammatory cytokines in the CM, further enhancing BMSC osteogenesis | The proinflammatory environment induced by GO promote osteogenic differentiation of BMSCs through OSM and NF-κB pathways |
| Wasnik S 2018 | C57BL/6 mice—BMSCs; C57BL/6 mice—Mφs | In vivo | Mice with the fracture at the midshaft receive a daily s.c. dose of 1,25(OH)2D | The suppression of fracture healing induced by 1,25(OH)2D is mediated by the inhibition of M1 Mφs during the proinflammatory stage | / |
| Nathan K 2019 | C57BL/6 mice—BMSCs; C57BL/6 mice—Mφs | In vitro | Coculture of BMSCs and M1 Mφs in the presence of IL-4 under the osteogenic induction medium | Temporal modulation of M1-to-M2 polarization maximizes MSC matrix mineralization | / |
| Tang H 2019 | Human—ADSCs; THP-1—Mφs | In vitro | M1 Mφs and ADSC coculture on PLGA/PCL scaffolds with osteogenic induction components | M1 Mφs inhibit the osteogenic differentiation of ADMSCs on 3D PLGA/PCL scaffolds | M1 Mφs inhibit osteogenic-related pathways (BMP & OSM signaling) during ADSC differentiation |
| Y He 2019 | SD rats—BMSCs; RAW 264.7—Mφs | In vitro & in vivo | In vitro: CM from Mφs seeded on Ti-SF/LL-37 is applied on BMSC culturing
In vivo: LL-37-loaded SFNPs of Ti rods are inserted into the bone defect | In vitro: osteogenic differentiation of BMSCs was enhanced by additional CM from Mφs incubated on Ti-SF/LL-37
In vivo: The Ti-SF/LL-37 group effectively induced both proinflammatory factors and exhibited improved osteogenesis ability | / |
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