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Deluca, A; Wagner, A; Heimel, P; Deininger, C; Wichlas, F; Redl, H; Rohde, E; Tempfer, H; Gimona, M; Traweger, A.
Synergistic effect of umbilical cord extracellular vesicles and rhBMP-2 to enhance the regeneration of a metaphyseal femoral defect in osteoporotic rats.
Stem Cell Res Ther. 2024; 15(1): 144
Doi: 10.1186/s13287-024-03755-8
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- Co-authors Med Uni Graz
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Deininger Christian
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- Abstract:
- BACKGROUND: The aim of this study was to evaluate potential synergistic effects of a single, local application of human umbilical cord MSC-derived sEVs in combination with a low dose of recombinant human rhBMP-2 to promote the regeneration of a metaphyseal femoral defect in an osteoporotic rat model. METHODS: 6 weeks after induction of osteoporosis by bilateral ventral ovariectomy and administration of a special diet, a total of 64 rats underwent a distal femoral metaphyseal osteotomy using a manual Gigli wire saw. Defects were stabilized with an adapted Y-shaped mini-locking plate and were subsequently treated with alginate only, or alginate loaded with hUC-MSC-sEVs (2 × 109), rhBMP-2 (1.5 µg), or a combination of sEVs and rhBMP-2 (n = 16 for each group). 6 weeks post-surgery, femora were evaluated by µCT, descriptive histology, and biomechanical testing. RESULTS: Native radiographs and µCT analysis confirmed superior bony union with callus formation after treatment with hUC-MSC-sEVs in combination with a low dose of rhBMP-2. This finding was further substantiated by histology, showing robust defect consolidation 6 weeks after treatment. Torsion testing of the explanted femora revealed increased stiffness after application of both, rhBMP-2 alone, or in combination with sEVs, whereas torque was only significantly increased after treatment with rhBMP-2 together with sEVs. CONCLUSION: The present study demonstrates that the co-application of hUC-MSC-sEVs can improve the efficacy of rhBMP-2 to promote the regeneration of osteoporotic bone defects.
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Animals - administration & dosage
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Bone Morphogenetic Protein 2 - pharmacology, genetics
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Recombinant Proteins - pharmacology, genetics
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Osteoporosis - pathology
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Rats - administration & dosage
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Female - administration & dosage
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Humans - administration & dosage
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Femur - pathology, drug effects, diagnostic imaging
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Umbilical Cord - cytology
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Extracellular Vesicles - metabolism
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Bone Regeneration - drug effects
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Rats, Sprague-Dawley - administration & dosage
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Transforming Growth Factor beta - pharmacology
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Disease Models, Animal - administration & dosage
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X-Ray Microtomography - administration & dosage
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Mesenchymal Stem Cells - metabolism
- Find related publications in this database (Keywords)
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BMP-2
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Extracellular vesicles
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Exosomes
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Drug delivery
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osteoporosis
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Metaphyseal defect