title: Priming Adipose Stem Cells with Tumor Necrosis Factor-Alpha Preconditioning Potentiates Their Exosome Efficacy for Bone Regeneration.
abstract: Mesenchymal stem cells (MSCs) have been widely used for tissue repair and regeneration. However, the inherent drawbacks, including limited cell survival after cell transplantation, have hindered direct MSC transplantation for tissue repair and regeneration. The aim of this study was to investigate if exosomes isolated from MSCs can promote the proliferation and differentiation of human primary osteoblastic cells (HOBs) and be potentially used for bone tissue regeneration. We showed that adipose tissue-derived MSC (ASC)-derived exosomes (ASC-EXO) were able to promote the proliferation and osteogenic differentiation in HOBs; and the trophic effects of ASC-EXO on HOBs were further harnessed when ASCs were preconditioned with tumor necrosis factor-alpha (TNF-α) for 3 days, which mimics the acute inflammatory phase upon bone injury. In addition, we showed that Wnt-3a content was elevated in ASC-EXO when ASCs were preconditioned by TNF-α, and inhibiting Wnt signaling decreased the osteogenic gene expression levels in HOBs which were cultured in TNF-α preconditioned ASCs conditioned medium. In conclusion, it was demonstrated that ASC-EXO, especially primed by TNF-α preconditioning on ASCs, offer a promising approach to replace direct stem cell transplantation for bone repair and regeneration.
authors.affiliation: Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney , Sydney, Australia .
authors.forename: ZuFu
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney , Sydney, Australia .
authors.forename: YongJuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney , Sydney, Australia .
authors.forename: Colin
authors.initials: C
authors.lastname: Dunstan
authors.affiliation: Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney , Sydney, Australia .
authors.forename: Seyediman
authors.initials: S
authors.lastname: Roohani-Esfahani
authors.affiliation: Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney , Sydney, Australia .
authors.forename: Hala
authors.initials: H
authors.lastname: Zreiqat
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D001861:Bone Regeneration / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D055354:Exosomes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D060509:Wnt3A Protein / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D014409:Tumor Necrosis Factor-alpha; D060509:Wnt3A Protein
keywords: TNF-α; Wnt-3a; bone regeneration; exosomes; stem cells