Investigating the role of apoptosis and tissue macrophages in mesenchymal stromal cell treatment of inflammatory lung diseases

Mesenchymal stromal cell (MSC) therapy is under intense clinical investigation due to the potential anti-inflammatory effects in a range of inflammatory diseases. However, there is limited understanding of the mechanism underlying MSC therapy. We found that impairing apoptosis in MSCs dampened their anti-inflammatory effects in vivo, rendering apoptosis necessary for the therapeutic effects of MSCs. We further showed that the spleen is indispensable for MSC-mediated immunosuppression. In the absence of splenic red pulp macrophages, the anti-inflammatory effects of MSCs are abolished in lung inflammation. Our data provide mechanistic insight into the mechanism underlying MSC therapy.