Low-intensity pulsed ultrasound combined with microbubbles enhances stem cell-based therapy for endometrial injury and intrauterine adhesion

Abstract

Low-intensity pulsed ultrasound (LIPUS) can repair damaged tissues via its biological effects on stem cells. Previous studies have shown that endometrial stem cells (EnSCs) can enhance the regeneration of damaged and promote uterine repair in mice with intrauterine adhesions (IUAs). However, whether low-intensity pulsed ultrasound combined with microbubbles (MBs) can promote the repair of IUA by EnSCs remains unclear. We established a mouse model of IUA in vivo via chemical injury method, and showed that the combination treatment improved the uterine structure of IUA, leading to endometrial thickening, an increased number of endometrial glands, decreased fibrosis, and microvascular hyperplasia; moreover, the expression level of vascular endothelial-related molecules (e.g., vascular endothelial growth factor, CD31) in the endometrium and CD44 molecules in the endothelial cells was increased, which ultimately improved the pregnancy outcome of IUA mice. To further validate the efficacy of the combined treatment of LIPUS and MBs, we demonstrated that the proliferative activity of EnSCs in the combined treatment group was increased by the in vitro CCK8 assay. Similarly, electron microscopy revealed that the number of lysosomes and ribosomes increased significantly, revealing that the combination treatment promoted the proliferation of EnSCs. The combination of LIPUS and MBs promotes endometrial injury repair, which may be related to its ability to promote the proliferation of EnSCs.