Extravascular Msc Treatment Induces Immunoregulatory Innate Immune Cells To Dampen Inflammation
Mesenchymal stromal cells (MSCs) have anti-inflammatory and tissue-reparative potentials. As such, MSCs present as a therapeutic cell type in inflammatory diseases. However, the mechanisms underlying their immunoregulatory effects are not well understood. MSC secretomes are thought to mediate their therapeutic effects. Recent studies from our lab and others highlighted MSC apoptosis in the lung following intravenous infusion, as a critical step in MSC-induced immunoregulation. MSCs administered via extravascular routes do not undergo apoptosis in the lung but have also been shown to exert therapeutic benefits. To investigate the mechanisms in extravascular administration of MSCs, we have established a mouse model of localised inflammation with lipopolysaccharide (LPS) and injected MSCs either directly at the site of inflammation (ipsilateral) or at the contralateral side. MSC treatment dampened inflammation by inducing an increase in IL-10-expressing immunoregulatory innate immune cells in the draining lymph nodes. Injected MSCs were detected only at the site of injection, yet induced an increase in immunosuppressive molecules, indoleamine 2,3-dioxygenase, in splenic myeloid population. This suggests the potential role of splenic immunoregulation in extravascular MSC treatment. Our data indicate that innate immune cells in the secondary lymphoid organs are important mediators of the anti-inflammatory effects of MSC treatment.