The protective effects of MSC-EXO against pulmonary hypertension through regulating Wnt5a/BMP signalling pathway

Area of Science:

• Cardiovascular Research
• Regenerative Medicine
• Cell Biology

Background:

• Pulmonary hypertension (PH) is a severe condition characterized by elevated pressure in pulmonary arteries.
• Current treatments for PH have limitations, necessitating the exploration of novel therapeutic strategies.
• Mesenchymal stem cells (MSCs) and their derived exosomes (MSC-EXO) have emerged as promising therapeutic agents.

Purpose of the Study:

• To investigate the protective mechanism of MSC-EXO against experimentally induced pulmonary hypertension (PH).
• To elucidate the role of the Wnt5a/BMP signaling pathway in MSC-EXO-mediated protection against PH.

Main Methods:

• A monocrotaline (MCT)-induced rat model of PH was established.
• Animals were treated with MSC-EXO via tail vein injection.
• In vitro experiments utilized hypoxia models of pulmonary artery endothelial cells (PAECs) and pulmonary vascular smooth muscle cells (PASMCs).
• Gene expression analysis was performed to assess signaling pathway components.

Main Results:

• MSC-EXO treatment significantly reduced right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index in vivo.
• MSC-EXO attenuated pulmonary vascular remodeling and lung fibrosis.
• In vitro, MSC-EXO treatment modulated the expression of Wnt5a, Wnt11, BMPR2, BMP4, BMP9, β-catenin, cyclin D1, and TGF-β1.
• Wnt5a siRNA transfection blocked the observed changes, indicating Wnt5a's crucial role.

Conclusions:

• MSC-EXO demonstrates significant therapeutic potential for treating pulmonary hypertension.
• The protective mechanism involves the regulation of the Wnt5a/BMP signaling pathway.
• MSC-EXO may represent a novel cell-free therapy for PH by modulating vascular remodeling.