Evaluating the defect targeting effects and osteogenesis promoting capacity of exosomes from 2D- and 3D-cultured human adipose-derived stem cells

Exosomes derived from stem cells show great therapeutic potential in bone defect repair. Systemic administration of exosomes represents as a minimally invasive delivery approach; however, evaluation for the lesion-targeting capacity and repair promotion efficacy lacks. In this study, exosomes produced by human adipose-derived stem cells (hADSCs) are intravenously injected to calvarial defect mice. It is found that exosomes preferentially accumulate at bone and especially at the calvarial defect site. In addition, exosomes treatment promotes osteogenesis as indicated by more newly formed bone at the lesion site. Furthermore, the impact of three-dimensional (3D) culture on hADSCs is evaluated by transcriptome sequencing and several pathways such as bone development, cartilage development are up-regulated in 3D-cultured hADSCs, suggesting an improved tissue repair capacity. Moreover, exosomes from 3D-cultured hADSCs show distinctly superior bone-targeting effects and bone repair capacity, as compared to those derived from 2D-cultured hADSCs. Collectively, this study highlights the bone-targeting and pro-osteogenic effects of hADSCs-derived exosomes, which could be further enhanced by 3D culture of the parental cells. Systemic injection of stem cell-derived exosomes could serve as a simple and minimally invasive approach to facilitate bone defect repair.