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

Stem Cells Transl Med. 2023 Mar 17;12(3):154-168. doi: 10.1093/stcltm/szad007.

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.

Keywords: endometrial fibrosis; exosomes; fibrosis biomarkers; intrauterine adhesions; poloxamer hydrogel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Collagen
  • Endometrium
  • Exosomes* / transplantation
  • Female
  • Fibrosis
  • Humans
  • Tissue Adhesions / drug therapy
  • Tissue Adhesions / pathology
  • Uterine Diseases* / pathology
  • Uterine Diseases* / therapy
  • Vimentin / therapeutic use

Substances

  • Biomarkers
  • Collagen
  • Vimentin