Stem cell therapy targets THBS1 to reverse endometrial fibrosis

Area of Science:

• Reproductive biology
• Cellular and molecular medicine
• Fibrosis research

Background:

• Intrauterine adhesions (IUA) cause female infertility and pregnancy loss due to endometrial fibrosis.
• The molecular mechanisms of IUA fibrosis are not fully understood.
• Thrombospondin-1 (THBS1), a matricellular protein, is implicated in fibrotic disorders but its role in IUA is understudied.

Purpose of the Study:

• To investigate the role of THBS1 in the pathogenesis of IUA.
• To evaluate the therapeutic potential of decidua-derived mesenchymal stem cells (DMSCs) in IUA.
• To explore the involvement of the PI3K/AKT signaling pathway in IUA and its modulation by THBS1 and DMSCs.

Main Methods:

• Transcriptomic profiling to identify upregulated genes in IUA tissues.
• In vitro and in vivo IUA models to assess fibrosis markers and signaling pathways (qPCR, Western blotting).
• Histological analysis (H&E, Masson staining) and quantification of inflammation and angiogenesis markers to evaluate therapeutic effects of THBS1 knockdown and DMSC treatment.

Main Results:

• THBS1 silencing reduced fibrotic markers and inhibited PI3K/AKT pathway activation in vitro.
• DMSC treatment demonstrated significant anti-fibrotic effects, suggesting THBS1 regulation.
• In vivo studies confirmed that THBS1 knockdown and DMSC administration alleviated fibrosis, reduced inflammation, and enhanced angiogenesis, improving endometrial structure.

Conclusions:

• THBS1 is a key pro-fibrotic factor in IUA, acting via the PI3K/AKT pathway.
• DMSCs mitigate IUA fibrosis and promote endometrial regeneration, likely through THBS1 downregulation.
• THBS1 represents a potential therapeutic target, and DMSCs show promise for IUA treatment.