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Review
. 2021 May 17:14:101093.
doi: 10.1016/j.bonr.2021.101093. eCollection 2021 Jun.

Mesenchymal stromal cell-derived extracellular vesicles for bone regeneration therapy

Vishnu Priya Murali  1 , Christina A Holmes  1
Affiliations
Review

Mesenchymal stromal cell-derived extracellular vesicles for bone regeneration therapy

Vishnu Priya Murali et al. Bone Rep. .

Abstract

Purpose: To analyze preclinical bone regeneration studies employing mesenchymal stromal cell (MSC)- derived extracellular vesicles (EVs) and highlight any commonalities in EV biomarker expression, miRNA cargo(s) or pathway activation that will aid in understanding the underlying therapeutic mechanisms.

Methods: Articles employing EVs derived from either MSCs or MSC-like osteogenic stromal cells in preclinical bone regeneration studies are included in this review.

Results: EVs derived from a variety of MSC types were able to successfully induce bone formation in preclinical models. Many studies failed to perform in-depth EV characterization. The studies with detailed EV characterization data report very different miRNA cargos, even in EVs isolated from the same species and cell types. Few preclinical studies have analyzed the underlying mechanisms of MSC-EV therapeutic action.

Conclusion: There is a critical need for mechanistic preclinical studies with thorough EV characterization to determine the best therapeutic MSC-EV source for bone regeneration therapies. Issues including controlled EV delivery, large scale production, and proper storage also need to be addressed before EV-based bone regeneration therapies can be translated for clinical bone repair.

Keywords: Biomaterials; Bone regeneration; Extracellular vesicles; Mesenchymal stromal cells; Tissue engineering; miRNA.

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Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Overview of common marker (green hexagons) and miRNA (orange hexagons) cargos carried by EVs derived from different MSC and MSC-like cell sources that demonstrated osteogenic potential in preclinical animal models.
Fig. 2
Fig. 2
Literature search results and screening process, based on PRISMA guidelines.
See this image and copyright information in PMC

References

    1. Ahluwalia A., Tarnawski A.S. Critical role of hypoxia sensor-HIF-1α in VEGF gene activation. Implications for angiogenesis and tissue injury healing. Curr. Med. Chem. 2012;19:90–97. - PubMed
    1. Amini Ami R., Laurencin Cato T., Nukavarapu Syam P. Bone tissue engineering: recent advances and challenges. Crit. Rev. Biomed. Eng. 2012;40:363. - PMC - PubMed
    1. Atienzar-Aroca Sandra, Flores-Bellver Miguel, Serrano-Heras Gemma, Martinez-Gil Natalia, Barcia Jorge M., Aparicio Silvia, Perez-Cremades Daniel, Garcia-Verdugo Jose M., Diaz-Llopis Manuel, Romero Francisco J. Oxidative stress in retinal pigment epithelium cells increases exosome secretion and promotes angiogenesis in endothelial cells. J. Cell. Mol. Med. 2016;20:1457–1466. - PMC - PubMed
    1. Baglio Serena Rubina, Rooijers Koos, Koppers-Lalic Danijela, Verweij Frederik J., Lanzón M. Pérez, Zini Nicoletta, Naaijkens Benno, Perut Francesca, Niessen Hans W.M., Baldini Nicola. Human bone marrow-and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species. Stem Cell Res Ther. 2015;6:127. - PMC - PubMed
    1. Baksh Dolores, Yao Raphael, Tuan Rocky S. Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells. 2007;25:1384–1392. - PubMed

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