Journal: Regenerative Therapy
Article Title: Recent progress in immunomodulation-based strategies for bone repair
doi: 10.1016/j.reth.2025.101054
Figure Lengend Snippet: Exosome-based immunomodulatory strategies for enhancing bone repair and regeneration. (A) Schematic illustration of the mechanism of M2 macrophage–derived exosomes (M2-Exos) in a diabetic fracture model. M2-Exos deliver immunoregulatory factors that suppress M1-driven pro-inflammatory responses, establish an anti-inflammatory microenvironment, and activate the PI3K/AKT signaling pathway, thereby improving bone repair. (B) In vitro experiments demonstrate that M2-Exos promote macrophage polarization toward an anti-inflammatory phenotype (upregulation of CD206, Arg-1, interleukin-10 [IL-10], CD163; downregulation of CD86) while enhancing the osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs), as indicated by increased alkaline phosphatase (ALP) activity and Alizarin Red staining. These findings suggest dual regulation of immunity and osteogenesis through intercellular communication. (C) In diabetic fracture mice, M2-Exos significantly improve histological repair at the fracture site (hematoxylin and eosin [HE] and Safranin O/Fast Green [SOFG] staining show enhanced new bone formation and reduced fibrous tissue deposition). Inhibition of the PI3K/AKT pathway attenuates these repair effects, validating the underlying molecular mechanism . Copyright 2023 ELSEVIER. (D) Bone morphogenetic protein-2 (BMP-2)–preconditioned BMSCs secrete exosomes (BMP2-Exos) with enhanced osteoinductive capacity. These exosomes deliver specific signaling molecules that promote MSC osteogenic differentiation and regulate immune cells (e.g., polarization of M2 macrophages), thereby accelerating angiogenesis and bone regeneration in defect models. (E) Histological and immunohistochemical analyses show that the BMP2-Exos group exhibits superior bone defect repair compared with controls, including faster bone bridge formation, increased bone matrix deposition, and upregulation of osteogenic proteins (RUNX2, osteocalcin [OCN], type I collagen [COL I]) and angiogenic markers (CD31, vascular endothelial growth factor [VEGF]) . Copyright 2024 ELSEVIER.
Article Snippet: Exosome-based immunomodulatory strategies for enhancing bone repair and regeneration. (A) Schematic illustration of the mechanism of M2 macrophage–derived exosomes (M2-Exos) in a diabetic fracture model. M2-Exos deliver immunoregulatory factors that suppress M1-driven pro-inflammatory responses, establish an anti-inflammatory microenvironment, and activate the PI3K/AKT signaling pathway, thereby improving bone repair. (B) In vitro experiments demonstrate that M2-Exos promote macrophage polarization toward an anti-inflammatory phenotype (upregulation of CD206, Arg-1, interleukin-10 [IL-10], CD163; downregulation of CD86) while enhancing the osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs), as indicated by increased alkaline phosphatase (ALP) activity and Alizarin Red staining.
Techniques: Derivative Assay, In Vitro, Activity Assay, Staining, Inhibition, Immunohistochemical staining
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![Exosome-based immunomodulatory strategies for enhancing bone repair and regeneration. (A) Schematic illustration of the mechanism of <t>M2</t> <t>macrophage–derived</t> exosomes <t>(M2-Exos)</t> in a diabetic fracture model. M2-Exos deliver immunoregulatory factors that suppress M1-driven pro-inflammatory responses, establish an anti-inflammatory microenvironment, and activate the PI3K/AKT signaling pathway, thereby improving bone repair. (B) In vitro experiments demonstrate that M2-Exos promote macrophage polarization toward an anti-inflammatory phenotype (upregulation of CD206, Arg-1, interleukin-10 [IL-10], CD163; downregulation of CD86) while enhancing the osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs), as indicated by increased alkaline phosphatase (ALP) activity and Alizarin Red staining. These findings suggest dual regulation of immunity and osteogenesis through intercellular communication. (C) In diabetic fracture mice, M2-Exos significantly improve histological repair at the fracture site (hematoxylin and eosin [HE] and Safranin O/Fast Green [SOFG] staining show enhanced new bone formation and reduced fibrous tissue deposition). Inhibition of the PI3K/AKT pathway attenuates these repair effects, validating the underlying molecular mechanism . Copyright 2023 ELSEVIER. (D) Bone morphogenetic protein-2 (BMP-2)–preconditioned BMSCs secrete exosomes (BMP2-Exos) with enhanced osteoinductive capacity. These exosomes deliver specific signaling molecules that promote MSC osteogenic differentiation and regulate immune cells (e.g., polarization of M2 macrophages), thereby accelerating angiogenesis and bone regeneration in defect models. (E) Histological and immunohistochemical analyses show that the BMP2-Exos group exhibits superior bone defect repair compared with controls, including faster bone bridge formation, increased bone matrix deposition, and upregulation of osteogenic proteins (RUNX2, osteocalcin [OCN], type I collagen [COL I]) and angiogenic markers (CD31, vascular endothelial growth factor [VEGF]) . Copyright 2024 ELSEVIER.](https://pub-med-central-images-cdn.bioz.com/pub_med_central_ids_ending_with_6002/pmc12796002/pmc12796002__gr4.jpg)