nn0c05122_si_001.pdf (252.5 kB)
Generation of Small RNA-Modulated Exosome Mimetics for Bone Regeneration
journal contribution
posted on 2020-09-11, 19:36 authored by Jiabing Fan, Chung-Sung Lee, Soyon Kim, Chen Chen, Tara Aghaloo, Min LeeAdministration of
exosomes is considered an attractive cell-free
approach to skeletal repair and pathological disease treatment. However,
poor yield for the production technique and unexpected therapeutic
efficacy of exosomes have been obstacles to their widespread use in
clinical practices. Here, we report an alternative strategy to produce
exosome-related vesicles with high yields and improved regenerative
capability. An extrusion approach was employed to amass exosome mimetics
(EMs) from human mesenchymal stem cells (hMSCs). The collected EMs
had a significantly increased proportion of vesicles positive for
the exosome-specific CD-63 marker compared with MSC-derived exosomes.
EMs were further obtained from genetically modified hMSCs in which
expression of noggin, a natural bone morphogenetic protein antagonist,
was down-regulated to enhance osteogenic properties of EMs. Moreover,
the administration of hMSC-EMs in conjunction with an injectable chitosan
hydrogel into mouse nonhealing calvarial defects demonstrated robust
bone regeneration. Importantly, mechanistic studies revealed that
the enhanced osteogenesis by EMs in which noggin was suppressed was
mediated via inhibition of miR-29a. These findings
demonstrate the great promise of MSC-mediated EMs and modulation of
small RNA signaling for skeletal regeneration and cell-free therapy.
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Keywords
miR -29abone regenerationBone Regeneration Administrationexosome-related vesiclesdisease treatmentproduction techniqueMSC-derived exosomesexosome-specific CD -63 markerprotein antagonistosteogenic propertiesextrusion approachexosome mimeticsmouse nonhealing calvarial defectsSmall RNA-Modulated Exosome Mimeticsinjectable chitosan hydrogelMSC-mediated EMsregenerative capabilityalternative strategy
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