Significance
Studies have confirmed that transplantation of exosomes exhibit similar therapeutic effects and functional properties to directly-transplanted stem cells but have less significant adverse effects. However, during in vitro culture conditions, MSCs are usually exposed to normoxia (21% O2) which is very different to the oxygen concentrations found in the body under natural physiological conditions. Our results demonstrated a mechanism by which Hypo-Exos promote bone fracture healing through exosomal miR-126 and the SPRED1/Ras/Erk signaling pathway. Moreover, hypoxia preconditioning mediated enhanced production of exosomal miR-126 through the activation of HIF-1α. Hypoxia preconditioning represents an effective and promising method for the optimization of the therapeutic actions of MSC-derived exosomes for bone fracture healing.
Statement of significance
Studies have confirmed that transplantation of exosomes exhibit similar therapeutic effects and functional properties to directly-transplanted stem cells but have less significant adverse effects. However, during in vitro culture conditions, MSCs are usually exposed to normoxia (21% O2) which is very different to the oxygen concentrations found in the body under natural physiological conditions. Our results demonstrated a mechanism by which Hypo-Exos promote bone fracture healing through exosomal miR-126 and the SPRED1/Ras/Erk signaling pathway. Moreover, hypoxia preconditioning mediated enhanced production of exosomal miR-126 through the activation of HIF-1α. Hypoxia preconditioning represents an effective and promising method for the optimization of the therapeutic actions of MSC-derived exosomes for bone fracture healing.