Extracorporeal Shock Wave Therapy Combined with Platelet-Rich Plasma during Preventive and Therapeutic Stages of Intrauterine Adhesion in a Rat Model

Abstract

Intrauterine adhesion (IUA) is caused by artificial endometrial damage during intrauterine cavity surgery. The typical phenotype involves loss of spontaneous endometrium recovery and angiogenesis. Undesirable symptoms include abnormal menstruation and infertility; therefore, prevention and early treatment of IUA remain crucial issues. Extracorporeal shockwave therapy (ESWT) major proposed therapeutic mechanisms include neovascularization, tissue regeneration, and fibrosis. We examined the effects of ESWT and/or platelet-rich plasma (PRP) during preventive and therapeutic stages of IUA by inducing intrauterine mechanical injury in rats. PRP alone, or combined with ESWT, were detected an increased number of endometrial glands, elevated vascular endothelial growth factor protein expression (hematoxylin-eosin staining and immunohistochemistry), and reduced fibrosis rate (Masson trichrome staining). mRNA expression levels of nuclear factor-kappa B, tumor necrosis factor-α, transforming growth factor-β, interleukin (IL)-6, collagen type I alpha 1, and fibronectin were reduced during two stages. However, PRP alone, or ESWT combined with PRP transplantation, not only increased the mRNA levels of vascular endothelial growth factor (VEGF) and progesterone receptor (PR) during the preventive stage but also increased PR, insulin-like growth factor 1 (IGF-1), and IL-4 during the therapeutic stage. These findings revealed that these two treatments inhibited endometrial fibrosis and inflammatory markers, thereby inhibiting the occurrence and development of intrauterine adhesions.

The predictive value of serum IL‐17A and IL‐6 expression in postoperative recurrence in patients with intrauterine adhesion

“…19 Several studies have reported that serum IL-6 levels are generally higher in IUA model mice than in normal mice. 20,21 Another cytokine connected with the immunological response is IL-17A. Its elevated levels can trigger an inflammatory response and exacerbate fibrosis.…”

“…IL‐6, a proinflammatory cytokine secreted by T cells and macrophages, stimulates the immune response and promotes fibrosis by regulating TGFβ signaling and stimulating fibroblast proliferation as well as collagen production 19 . Several studies have reported that serum IL‐6 levels are generally higher in IUA model mice than in normal mice 20,21 . Another cytokine connected with the immunological response is IL‐17A.…”

Frontier Review of the Molecular Mechanisms and Current Approaches of Stem Cell-Derived Exosomes

“…Being the implant sites of blastocytes, endometrium undoubtedly plays a crucial role in female pregnancy. Asherman’s syndrome, also called intrauterine adhesion (IUA), is characterized by poor glandular epithelial growth and vascular development from scarring, and fibrosis primarily caused by artificial trauma, repeated endometritis, and infection [ 59 , 73 , 74 ]. Endometrial fibrosis causes a loss of regeneration competence in functional endometrium, which eventually leads to secondary infertility, the most common type of infertility worldwide [ 60 , 75 ].…”

Biomaterializing the advances in uterine tissue engineering

“…G-CSF has been used in some studies to demonstrate contradictory efficacy. 122 According to the findings of Zadehmodarres’ pilot study, platelet-rich plasma promotes endometrial growth in patients with thin endometrium and pregnancy in infertile patients. 123 Dogras et al.…”

“…demonstrated that extracorporeal shock wave therapy can improve its efficacy by collaborating with platelet-rich plasma. 122 These measures can be used in conjunction with uterine tissue engineering, but severe injuries such as partial or subtotal hysterectomy still necessitate more sophisticated tissue engineering systems.…”