Microfluidic chip-integrated vascularized endometrial complexes: Mitochondrial function and paracrine crosstalk...

Area of Science:

• Reproductive Biology
• Biomedical Engineering
• Tissue Engineering

Background:

• Endometrial injury impacts fertility and women's health.
• Existing endometrial organoids lack the complexity of in vivo tissue.
• There is a need for more physiologically relevant models for studying endometrial function and repair.

Purpose of the Study:

• To develop a vascularized triple-cellular endometrial complex.
• To assess its efficacy in endometrial repair and fertility improvement.
• To elucidate the paracrine mechanisms driving its regenerative properties.

Main Methods:

• Integration of endometrial epithelial organoids, stromal cells, and endothelial cells in a microfluidic chip.
• Utilizing a composite hydrogel (Matrigel and fibrin) for tissue support.
• Evaluation in an immunodeficient mouse model of endometrial damage.
• Single-cell RNA sequencing to analyze cellular interactions.

Main Results:

• The vascularized endometrial complex demonstrated robust growth and repair capabilities.
• Significant improvement in pregnancy rates was observed in the mouse model.
• Single-cell RNA sequencing revealed bidirectional paracrine crosstalk between cell types.
• Specific signaling pathways (BMP6, Galectin-9, WNT7A, WNT5A) were identified as crucial for regeneration and angiogenesis.

Conclusions:

• The vascularized triple-cellular endometrial complex shows superior regenerative properties for endometrial repair.
• This model offers a promising therapeutic strategy for infertility associated with endometrial damage.
• It serves as a valuable in vitro platform for studying endometrial pathophysiology.