Endothelin-1 governs proliferation and migration of bronchoalveolar lavage-derived lung mesenchymal stem cells in bronchiolitis obliterans syndrome.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) has an incidence of 57% at 5 years after lung transplantation, accounts for 30% of all deaths 3 years posttransplant and because treatment options are extremely limited, it constitutes a significant health care problem. Adult mesenchymal stem cells (MSCs) play a role in lung turnover; however, their role in BOS remains unknown.
METHODS: MSCs were isolated from bronchoalveolar lavage (BAL) in 101 lung allograft recipients. BAL was screened by protein array and MSCs were analyzed by real-time polymerase chain reaction, proliferation, migration, and enzyme linked immunosorbent assays.
RESULTS: Multipotent MSCs were isolated from BAL of lung recipients independent of BOS presence. However, MSCs from BOS patients proliferated at higher rates (P<0.001) and were associated with higher α-smooth muscle actin (P = 0.03) but lower surfactant protein B (P = 0.02) compared with those from no-BOS patients. Histological analysis revealed that MSCs are abundant in lung tissue of BOS patients. MSCs from BOS patients produced higher endothelin-1 (ET-1) amounts (P<0.001) compared with those from no-BOS; and ET-1 stimulated whereas ET-1 blockade suppressed MSC proliferation, migration, and differentiation.
CONCLUSIONS: These results indicate that MSCs are associated with BOS and are governed by ET-1. Targeting MSCs by ET-1 blockade might be useful in BOS treatment.