# Stem cell therapy targets THBS1 to reverse endometrial fibrosis

## TL;DR

This study shows that targeting THBS1 with stem cell therapy can reverse fibrosis in the uterus, offering a new treatment for infertility caused by intrauterine adhesions.

## Contribution

The study identifies THBS1 as a key driver of fibrosis in IUA and demonstrates that DMSCs can reverse fibrosis by modulating THBS1 and the PI3K/AKT pathway.

## Key findings

- THBS1 is significantly upregulated in IUA tissues and promotes fibrosis via the PI3K/AKT pathway.
- DMSC treatment reduces fibrosis, inflammation, and enhances angiogenesis in IUA models.
- THBS1 knockdown and DMSC administration both improve endometrial structure and reduce collagen deposition.

## Abstract

Intrauterine adhesions (IUA) are a major cause of female infertility and recurrent pregnancy loss, characterized by endometrial fibrosis. The molecular mechanisms underlying IUA fibrosis are poorly understood. Thrombospondin-1 (THBS1), a matricellular protein linked to fibrotic disorders, has not been extensively studied in IUA. This study investigates the role of THBS1 in IUA pathogenesis and the therapeutic potential of decidua-derived mesenchymal stem cells (DMSCs), focusing on the PI3K/AKT signaling pathway.

Transcriptomic profiling identified significant upregulation of THBS1 in IUA tissues. Pathway analysis suggested that THBS1 promotes fibrosis via the PI3K/AKT pathway. In vitro and in vivo IUA models were used to evaluate fibrosis markers and signaling molecules using qPCR and Western blotting. The therapeutic effects of DMSCs and THBS1 knockdown were assessed through histological analyses (H&E and Masson staining) and quantification of inflammation and angiogenesis markers.

THBS1 silencing reduced fibrotic markers and inhibited PI3K/AKT pathway activation in vitro. DMSC treatment showed a more pronounced anti-fibrotic effect, suggesting that DMSC-mediated repair involves THBS1 regulation. In vivo, both THBS1 knockdown and DMSC administration alleviated intrauterine fibrosis, reduced inflammation, and enhanced angiogenesis. Histological evaluations confirmed improved endometrial structure and reduced collagen deposition, especially in DMSC-treated and combination therapy groups.

THBS1 is a key pro-fibrotic factor in IUA, modulating the PI3K/AKT pathway. DMSCs effectively mitigate fibrosis and promote endometrial regeneration, potentially by downregulating THBS1. This study highlights THBS1 as a promising therapeutic target and reinforces the clinical potential of DMSCs for IUA treatment.