Protective effects of adipose stem cells against cigarette‐smoke induced lung injury

Abstract

Adipose‐derived stem cells (ASCs) express several critical determinants of lung rejuvenation, thus providing components necessary for tissues to recover from lung injury, such as that induced by cigarette smoke (CS) in emphysema. We evaluated the therapeutic effects of ASCs on CS‐induced lung injury. Mice were exposed to CS for 4 months; during the second half of CS exposure, mice were treated with 3.5 x 105 murine ASCs or saline (i.v. qow). Mice receiving ASCs were protected against CS‐induced alveolar space enlargement, measured by mean linear intercept (mean=30.72; sem=0.779; p=0.032). This effect was associated with decreased PMN lung inflammation, as well as AKT and p38 MAPK activation induced by CS exposure (p=0.028 and 0.0311). Alveolar (endothelial) cell barrier dysfunction may be an early injury marker induced by CS in the lung. Since ASCs are known to secrete vascular‐protective factors, we tested the ability of ASC supernatants to protect against CS‐induced endothelial cell permeability. CS caused a dose‐dependent decrease in primary mouse trans‐endothelial monolayer electrical resistance (64% at 5hr) that was significantly attenuated by ASC‐ media and by a specific p38 MAPK inhibitor (p=0.034 and 0.004). These results suggest a protective effect of ASCs from CS‐induced lung injury that may involve paracrine modulation of the AKT and p38 signaling pathways. Funding: IU Signature Center Grant.