Synergistic Effect of Umbilical Cord Extracellular Vesicles and RhBMP-2 to Enhance the Regeneration of a Metaphyseal Femoral Defect in Osteoporotic Rats

Overview

Journal Stem Cell Res Ther

Publisher Biomed Central

Date 2024 May 19

PMID 38764077

Authors

Amelie Deluca

Andrea Wagner

Patrick Heimel

Christian Deininger

Florian Wichlas

Heinz Redl

Eva Rohde

Herbert Tempfer

Mario Gimona

Andreas Traweger

Affiliations

Soon will be listed here.

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 × 10), 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.

Citing Articles

Therapeutic Efficacy and Promise of Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles in Aging and Age-Related Disorders.

Zhang A, Li Q, Chen Z Int J Mol Sci. 2025; 26(1.

PMID: 39796081 PMC: 11719504. DOI: 10.3390/ijms26010225.

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