Research & Innovation
Publications
Synergistic effect of umbilical cord extracellular vesicles and rhBMP-2 to enhance the regeneration of a metaphyseal femoral defect in osteoporotic rats
PMU Authors
Andrea Wagner, Christian Deininger, Florian Wichlas, Eva Rohde, Herbert Tempfer, Mario Gimona, Andreas Traweger
All Authors
Amelie Deluca, Andrea Wagner, Patrick Heimel, Christian Deininger, Florian Wichlas, Heinz Redl, Eva Rohde, Herbert Tempfer, Mario Gimona, Andreas Traweger
Journal association
Stem cell research & therapy
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 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