Forschung & Innovation
Publikationen
Synergistic effect of umbilical cord extracellular vesicles and rhBMP-2 to enhance the regeneration of a metaphyseal femoral defect in osteoporotic rats
PMU Autor*innen
Andrea Wagner, Christian Deininger, Florian Wichlas, Eva Rohde, Herbert Tempfer, Mario Gimona, Andreas Traweger
Alle Autor*innen
Amelie Deluca, Andrea Wagner, Patrick Heimel, Christian Deininger, Florian Wichlas, Heinz Redl, Eva Rohde, Herbert Tempfer, Mario Gimona, Andreas Traweger
Fachzeitschrift
Stem cell research & therapy
Kurzfassung
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 x 109), rhBMP-2 (1.5 mu g), or a combination of sEVs and rhBMP-2 (n = 16 for each group). 6 weeks post-surgery, femora were evaluated by mu CT, descriptive histology, and biomechanical testing. Results Native radiographs and mu CT 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.
Keywords
Humans, Female, Animals, Mesenchymal Stem Cells/metabolism, Femur/pathology, RATS, Rats, Sprague-Dawley, Disease Models, Animal, Bone Morphogenetic Protein 2/pharmacology, Recombinant Proteins/pharmacology, Osteoporosis/pathology, Umbilical Cord/cytology, Extracellular Vesicles/metabolism, Bone Regeneration/drug effects, Transforming Growth Factor beta/pharmacology, X-Ray Microtomography