Engineered BMP2/BMP7 extracellular vesicles induce autocrine BMP release driving SMAD phosphorylation to promote bone formation
Abstract In the United States, impaired bone healing impacts ~600,000 patients annually. Bone morphogenetic protein 2 (rhBMP2) therapy is impeded by low bone quality and adverse effects. Here, mesenchymal stem cells, engineered to produce BMP2 and BMP2/7 containing extracellular vesicles (BMP2-EV an...
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| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-06-01
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| Series: | npj Regenerative Medicine |
| Online Access: | https://doi.org/10.1038/s41536-025-00405-2 |
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| Summary: | Abstract In the United States, impaired bone healing impacts ~600,000 patients annually. Bone morphogenetic protein 2 (rhBMP2) therapy is impeded by low bone quality and adverse effects. Here, mesenchymal stem cells, engineered to produce BMP2 and BMP2/7 containing extracellular vesicles (BMP2-EV and BMP2/7-EV), provided an alternative means of stimulating bone formation. BMP2-EV and BMP2/7-EV drove increased calcium deposition and alkaline phosphatase activity; with increase in osterix, RUNX2, osteocalcin, and osteopontin documenting osteoblast differentiation. BMP2/7-EV induced SMAD phosphorylation and calcium deposition, was inhibited by DMH1, a BMP I receptor inhibitor, demonstrating BMP receptor dependence. BMP2 and BMP7 extracellular vesicle encapsulation was confirmed with preserved potency following treatment with BMP antagonist, Noggin. Application of BMP2/7-EV in a rat calvarial defect model demonstrated enhanced bone formation on micro-computed tomography and histopathologic analysis, equaling rhBMP2. BMP2/7-EV mediated bone formation here highlights EVs as a unique modality for delivery of tailored polyvalent regenerative biotherapies. |
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| ISSN: | 2057-3995 |