The mechanism of adipose mesenchymal stem cells to stabilize the immune microenvironment of pelvic floor injury by regulating pyroptosis and promoting tissue repair

Xiaotong Wu; Fengshi Zhang; Xiaolin Mao; Fujian Xu; Xiaokang Ding; Xiuli Sun; Jianliu Wang

doi:10.1016/j.mtbio.2023.100910

The mechanism of adipose mesenchymal stem cells to stabilize the immune microenvironment of pelvic floor injury by regulating pyroptosis and promoting tissue repair

Mater Today Bio. 2023 Dec 18:24:100910. doi: 10.1016/j.mtbio.2023.100910. eCollection 2024 Feb.

Authors

Xiaotong Wu^{1

2}, Fengshi Zhang³, Xiaolin Mao⁴, Fujian Xu⁴, Xiaokang Ding⁴, Xiuli Sun^{1

2}, Jianliu Wang^{1

2}

Affiliations

¹ Department of Obstetrics and Gynecology, Peking University People's Hospital, 100044, Beijing, China.
² Beijing Key Laboratory of Female Pelvic Floor Disorders, 100044, Beijing, China.
³ Department of Orthopedics and Trauma, Peking University People's Hospital, 100044, Beijing, China.
⁴ College of Materials Science and Engineering, Beijing University of Chemical Technology, 100029, Beijing, China.

Abstract

Pelvic organ prolapse (POP) has a high incidence rate among Chinese women. Repeated mechanical stimulation is an important factor causing POP, but the injury mechanism has not yet been elucidated. The purpose of this study is to explore the related mechanisms of pelvic floor supporting tissue damage caused by mechanical force and the application of stem cell therapy. First, we obtained vaginal wall and sacral ligament tissue samples from clinical patients for examination. Pelvic floor support tissues of POP patients displayed high expression of inflammation and immune disorders. Then, we constructed a rat model of childbirth injury. In vivo and in vitro experiments investigated the key mechanism of pelvic floor support tissue injury caused by mechanical force. We discovered that after mechanical force, a large number of reactive oxygen species (ROS) and macrophages rapidly accumulated in pelvic floor tissues. ROS stimulated macrophages to produce NLRP3 inflammatory complex, induced the release of interleukin (IL-1β) and pyroptosis and exacerbated the inflammatory state of damaged tissues, persisting chronic inflammation of fibroblasts in supporting tissues, thus causing the pelvic floor's extracellular matrix (ECM) collagen metabolic disorder. Resultingly impeding the repair process, thereby causing the onset and progression of the disease. Through their paracrine ability, we discovered that adipose mesenchymal stem cells (ADSCs) could inhibit this series of pathological processes and promote tissue repair, asserting a good therapeutic effect. Simultaneously, to overcome the low cell survival rate and poor therapeutic effect of directly injecting cells, we developed a ROS-responsive PVA@COLI hydrogel with ADSCs. The ROS-scavenging properties of the gel could reshape the site of inflammation injury, enhance cell survival, and play a role in subsequent treatment. The findings of this study could serve as a basis for early, targeted intervention therapy for POP and representing a promising approach.

Keywords: ADSCs; Antioxidant; Immune regulation; Mechanical force; Pyroptosis.