Delivery of High Mobility Group Box-1 via Engineered Exosomes Improves Cavernosa I njury -Induced Erectile Dysfunction in Rats

Abstract BackgroundCavernous is a vascular-rich tissue. Thus, vascular reconstruction is suggested to be essential for the treatment of erectile dysfunction (ED) caused by cavernosa injury. High mobility group box-1 (HMGB1) has been involved in the regulation of growth and differentiation of vascular endothelial cell. In this study, the therapeutic efficiency of engineering HMGB1/Exosomes (exos) derived from adipose tissue derived stem cells (ADSCs) were determined on injured cavernosa.MethodsWe constructed engineered HMGB1/exos and CD63-HMGB1/exos derived from ADSCs. MTT assay, migration assay, and angiogenesis assay were performed in vitro, and erectile and vascular function were detected in a mouse model.ResultsHMGB1 could be successfully delivered to human umbilical venous endothelial cells (HUVECs) via engineered CD63-HMGB1/exos. Treatment with CD63- HMGB1/exos resulted in a significant increase in the proliferation, migration, and angiogenesis of HUVECs. In vivo experiments showed that rats of CD63- HMGB1/exos group had the highest ICP/MAP values at 14 and 28 days after injection. Meanwhile, treatment of CD63- HMGB1/exos remarkably increased the content of smooth muscle. The expression of CD31and vascular endothelial factors were increased after the treatment of CD63-HMGB1/exos, which indicating improved vascular function.ConclusionsEngineering CD63- HMGB1/exos derived from ADSCs notably repaired injured cavernosa-induced ED via promoting vascular reconstruction.