Exosome-Based Regimen Rescues Endometrial Fibrosis in Intrauterine Adhesions Via Targeting Clinical Fibrosis Biomarkers

Abstract

Intrauterine adhesions (IUA), which is characterized by endometrial fibrosis, continue to be the most common cause of uterine infertility globally. Our work revealed that 3 fibrotic progression markers (Vimentin, COL5A2, and COL1A1) were significantly increased in the endometrium of IUA patients. Mesenchymal stem cell–derived exosomes (EXOs) have been recently revealed as a cell-free therapy for fibrosis diseases. Nevertheless, the application of EXOs is restricted by the short residency duration in the target tissue. To overcome this limitation, herein, we reported an exosome–based regimen (EXOs-HP) that thermosensitive poloxamer hydrogel possessed the ability to efficiently promote the residency duration of EXOs in the uterine cavity. By downregulating fibrotic progression markers (Vimentin, COL5A2, and COL1A1), EXOs-HP could significantly restore the function and structure of the injured endometrium in the IUA model. Our work provides the theoretical and experimental foundation of EXOs-HP in treating IUA, highlighting the clinical potential of topical EXOs-HP delivery system in IUA patients.

Secretion of WNT7A by UC-MSCs assist in promoting the endometrial epithelial regeneration

“…Furthermore, compared with that in the uterine injury group, we observed increased expression of the endometrial stromal cell marker vimentin in the UC-MSC+hydrogel group, hydrogel group and UC-MSC group, which were close to the result in the blank group, indicating improved endometrial regeneration in the rats ( Figures S2 I and S2J; uterine injury vs. hydrogel vs. UC-MSC vs. UC-MSC+hydrogel vs. blank; 76.5 ± 40.0 vs. 114.1 ± 18.4 vs. 110.0 ± 13.9 vs. 123.9 ± 12.4 vs. 128.1 ± 11.6, respectively). 5 , 34 , 35 , 36 , 37 , 38 …”

“…Moreover, the endometrial morphology indicated significant recovery of the uterine injury in the rat model treated with hydrogel-loaded UC-MSCs, accompanied by a notable reduction in fibrosis and successful restoration of the regenerative capacity within the endometrium. 1 , 5 , 35 …”

TSG6‐Exo@CS/GP Attenuates Endometrium Fibrosis by Inhibiting Macrophage Activation in a Murine IUA Model

“…Studies show that the application of thermosensitive hydrogels reduces endometrial injury. [66] To further improve the therapeutic efficacy, we developed injectable thermosensitive hydrogels (CS/GP) capable of encapsulating TSG6-modified Exos (TSG6-Exo@CS/GP). This innovative approach enabled targeted delivery of TSG6-modified-Exos to the uterine cavity, ensuring sustained release and timely administration.…”

Mechanism study of BMSC-exosomes combined with hyaluronic acid gel in the treatment of posttraumatic osteoarthritis

“…Variability in exosome functionality and stability across different samples and storage conditions necessitates further research for clinical application. Establishing standardized and scalable production processes is imperative for consistent and replicable exosome-based therapies [ 56 , 57 ].…”