2. Academic Validation
  3. Telocyte-Derived Exosomes Provide an Important Source of Wnts That Inhibits Fibrosis and Supports Regeneration and Repair of Endometrium

Telocyte-Derived Exosomes Provide an Important Source of Wnts That Inhibits Fibrosis and Supports Regeneration and Repair of Endometrium

  • Cell Transplant. 2023 Jan-Dec:32:9636897231212746. doi: 10.1177/09636897231212746.
Tian-Quan Chen 1 2,  Xiao-Jiao Wei 1,  Hai-Yan Liu 2,  Sheng-Hua Zhan 3,  Xiao-Jun Yang 1
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • 2 Department of Obstetrics and Gynecology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
  • 3 Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China.
PMID: 38006220 DOI: 10.1177/09636897231212746
Abstract

Intrauterine adhesions (IUAs) often occurred after common obstetrical and gynecological procedures or infections in women of reproductive age. It was characterized by the formation of endometrial fibrosis and prevention of endometrial regeneration, usually with devastating fertility consequences and poor treatment outcomes so far. Telocytes (TCs), as a novel interstitial cell type, present in female uterus with in vitro therapeutic potential in decidualization-defective gynecologic diseases. This study aims to further investigate the role of TC-derived Wnt ligands carried by exosomes (Exo) in reversal of fibrosis and enhancement of regeneration repair in endometrium. IUA cellular and animal models were established from endometrial stromal cells (ESCs) and mice, followed with treatment of TC-conditioned medium (TCM) or TC-derived Exo. In cellular model, fibrosis markers (collagen type 1 alpha 1 [COL1A1], fibronectin [FN], and α-smooth muscle actin [α-SMA]), angiogenesis (vascular endothelial growth factor [VEGF]), and pathway protein (β-catenin) were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting (WB), and immunofluorescence. Results showed that, TCs (either TCM or TC-derived Exo) provide a source of Wnts that inhibit cellular fibrosis, as evidenced by significantly elevated VEGF and β-catenin with decreased fibrotic markers, whereas TCs lost salvage on fibrosis after being blocked with Wnt/β-catenin inhibitors (XAV939 or ETC-159). Further in mouse model, regeneration repair (endometrial thickness, number of glands, and fibrosis area ratio), fibrosis markers (fibronectin [FN]), mesenchymal-epithelial transition (MET) (E-cadherin, N-Cadherin), and angiogenesis (VEGF, microvessel density [MVD]) were studied by hematoxylin-eosin (HE), Masson staining, and immunohistochemistry. Results demonstrated that TC-Exo treatment effectively promotes regeneration repair of endometrium by relieving fibrosis, enhancing MET, and angiogenesis. These results confirmed new evidence for therapeutic perspective of TC-derived Exo in IUAs.

Keywords

endometrial stromal cells (ESCs); exosome (Exo); fibrosis; intrauterine adhesions (IUAs); telocytes (TCs).

Figures
Products