Adipose Mesenchymal Stem Cells Overexpressing Chemokine (CXCL6) Showed Strong Angiogenesis and Anti-Inflammatory Ability in the Treatment of Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling and right ventricular failure, with limited effective treatments. This study aimed to evaluate therapeutic effects of adipose-derived mesenchymal stem (ADMS) cells engineered to overexpress chemokine CXCL6 in monocrotaline-induced PAH rats. ADMS cells were transduced with a CXCL6-expressing lentivirus and characterized by flow cytometry, migration assays, and tube formation tests. Following establishment of PAH model, rats were administered intravenous injections of CXCL6-ADMS or control cells. Pulmonary arterial pressure was measured using a polyethylene cannula advanced to right ventricle, and right ventricular hypertrophy was quantitatively evaluated by weight ratio of right ventricle to left ventricle plus septum. Histopathological analysis and quantitative PCR were conducted to assess vascular injury and inflammation. ELISA was utilized to quantify inflammatory mediators in serum. CXCL6 transduction yielded ≈ 52% infection efficiency and preserved ADMS phenotype while significantly enhancing migration (≈ 1.3-fold) and tube formation (≈ 78% increase) vs. unmodified ADMSCs (p < 0.05). In vivo, CXCL6-ADMS treatment significantly reduced mean pulmonary arterial pressure and RV hypertrophy (RV/LV+S) compared with PAH and ADMSC groups (p < 0.05), and markedly attenuated pulmonary inflammation and vascular remodeling on histology (p < 0.05). Molecular analyses showed significant upregulation of eNOS and apelin and downregulation of NOX2, NOX4, MCP-1, Vascular Endothelial Growth Factor (VEGF) and Hepatocyte Growth Factor (HGF) in lung and heart tissues after CXCL6-ADMSC therapy (p < 0.05). Serum TNF-α decreased while several pro-angiogenic mediators were modulated (p < 0.05). CXCL6-ADMS cells may offer a promising therapeutic intervention for PAH by modulating vascular inflammation and remodeling. Further clinical investigations are necessary to confirm these results.