BMSCs transplantation combined with LIPUS treatment improves erectile function through downregulation of IGFBP3 in rats with cavernosa injury

Abstract Background Erectile dysfunction (ED) is the most common type of sexual dysfunction, which seriously affects male reproductive health. Recently, stem cell therapy and low‐intensity pulsed ultrasound (LIPUS) have been applied in the treatment of ED, but the specific mechanism is still unclear. Objectives The study aims to investigate the effect and underlying mechanism of further LIPUS treatment on the basis of bone marrow mesenchymal stem cells (BMSCs) transplantation in the treatment of ED rats. Materials and methods We established a cavernosa injury‐induced ED rat model and injected BMSCs into the penile corpus cavernosum with or without LIPUS treatment every other day for three times. The survival rate of BMSCs, value of ICP/MAP, blood flow, the endothelial content, and expression of CD31 and ɑ‐SMA in the rat penis were investigated. Transcriptome analyses and in vitro assays of cell proliferation, migration, and tube formation were also performed. Results The results showed that LIPUS treatment significantly promoted the survival rate of BMSCs in the rat penis after 1, 7, and 14 days of final treatment. The values of ICP/MAP and blood flow in rats treated with BMSCs were significantly increased compared to the control group, and the values were further enhanced in rats treated with BMSCs plus LIPUS. The endothelial content and CD31 and ɑ‐SMA mRNA and protein expression in the BMSCs plus LIPUS group were remarkably higher than in other groups, indicating improved endothelial vascular function. Transcriptome analyses found that insulin‐like growth factor binding protein‐3 (IGFBP3) was remarkably downregulated in the BMSCs plus LIPUS group compared to the other two groups. In in vitro assays, LIPUS intervention significantly increased BMSCs proliferation and HUVECs migration, and HUVECs angiogenesis was improved after IGFBP3 siRNA transfection. Conclusions BMSCs transplantation combined with LIPUS treatment could improve erectile function in ED rats via downregulation of IGFBP3, which might be a proposed optimized strategy for the ED treatment.