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| Author | Cell source | Study type | Cell management | Immunoregulatory potential of MSCs on Mφs | Proposed mechanisms |
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| Tasso R 2013 | C57BL/6 mice—BMSCs; C57BL/6 mice—Mφs | In vitro & in vivo | In vitro: Mφs cultured in the IL-1a-stimulated BMSC-CM
In vivo: BMSCs seeded on bioceramic scaffolds are transplanted | In vitro: the percentage of M2 Mφs significantly increases after Mφs cultured in the CM from BMSCs
In vivo: implanted BMSCs induce Mφ switching to a proresolving phenotype and recruit vasculogenic and osteogenic progenitors from BM | PGE2 secreted from BMSCs activates the NF-κB pathway to affect M2 Mφ polarization |
| Seebach E 2014 | SD rats—BMSCs; SD rats—Mφs | In vivo | BMSCs embedded in a fibrin carrier are implanted into femoral bone defects | BMSC composites attract proinflammatory M1 Mφs and endothelial progenitors and then promote implant integration, angiogenesis, and tissue maturation | / |
| Tour G 2014 | Lewis GFP transgenic rat—BMSCs; SD rats—Mφs | In vivo | BMSCs with HA-ECM are implanted into calvarial bone defects | M1 Mφs were prevalent than M2 Mφs in the calvarial defects at 2 weeks after surgery | / |
| Lin T 2017 | C57BL/6 mice—BMSCs; C57BL/6 mice—Mφs | In vitro | Mφs are treated with the CM from LPS-exposed MSCNF-κBREIL4 | CM from MSCNF-κBREIL4 modulates inflammatory M1 Mφs into an anti-inflammatory M2 Mφs | NF-κB-sensing MSCNF-κBREIL4 produces excessive IL-4 for immunomodulation |
| Lin T 2017 | C57BL/6 mice—BMSCs; C57BL/6 mice—Mφs | In vitro | Preconditioned BMSCs with LPS plus TNF-α culture with M1 Mφs | Preconditioned BMSCs modulate M1 Mφs into an anti-inflammatory phenotype and increase PGE2 production but not affect mineralization | Preconditioned BMSC-secreted PGE2 can be stimulated by TNF-α through the NF-κB/COX2-dependent pathway |
| Saldana L 2017 | Human—BMSCs; THP-1—Mφs | In vitro | BMSCs undergo osteogenic differentiation with the CM from the cocultures of BMSCs, Mφs, and 1,25D3 | 1,25D3 promotes the switching of cocultured Mφs toward the M2 phenotype secreting anti-inflammatory factors (IL-10, PGE2) to enhance matrix maturation and mineralization of BMSCs | / |
| Li T 2018 | SD rats—BMSCs; RAW 264.7—Mφs | In vitro & in vivo | In vitro: Lap/Mφ CM with osteogenic components is applied to stimulate BMSCs
In vivo: Lap+BMSCs are injected into the bone defect | In vitro: BMSCs reversed M1 Mφs induced by Lap into M2 Mφs and promoted osteogenesis
In vivo: the Lap+BMSC group shows obvious new bone formation with a significant increase in M2 Mφs | Activation of the OSM pathway is likely involved in the enhanced osteogenesis by BMSCs |
| He Y 2019 | SD rats—BMSCs; RAW 264.7—Mφs | In vitro & in vivo | In vitro: CM from BMSCs seeded on Ti-SF/LL-37 is applied on Mφ culturing
In vivo: LL-37-loaded SFNPs of Ti rods are inserted into the bone defect | In vitro: M2 phenotype switching of Mφs is induced by the BMSCs seeded on Ti-SF/LL-37
In vivo: demonstrated in Table 2 | / |
| Wei F 2019 | Human—BMSCs; RAW 264.7—Mφs | In vitro | LPS-induced Mφs are treated with exosomes first isolating from osteogenically differentiating BMSCs | The uptake of exosomes significantly decreases the M1 phenotypic marker of LPS-induced Mφs | / |
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