Investigating the antibacterial effect of Sca1+ lung mesenchymal stem cells on multidrug resistant bacterial species

Abstract

Abstract Rationale Although bone marrow-derived mesenchymal stem cells have been extensively studied in host protection against bacterial pneumonia, the role of lung stem/mesenchymal stem cells in pneumonia caused by the multidrug-resistant bacteria remains elusive. Methods We have compared the extracellular (using 10 MOI) and intracellular (using 1 MOI) killing effects of stem cell antigen 1+ lung mesenchymal stem cells (Sca1+ LMSC), bone marrow-derived neutrophils (BMDN), and bone marrow-derived macrophages (BMDM) by infecting them with Gram positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram negative carbapenem-resistant Klebsiella pneumoniae (CRKP) at different time points. We evaluated the extracellular and intracellular killing at each time point by plating them on Tryptic soy agar and MacConkey agar plates, respectively. We also have examined expression of inflammasomes or inflammasome-associated proteins in MRSA (20 MOI for 6 h) infected LMSC using Western blotting. Results Sca1+ LMSC is potent in killing (extracellular) both MRSA and CRKP at 3 h post-infection. However, BMDN did not show significant extracellular killing on MRSA and CRKP at all time points examined. Interestingly, Sca1+ LMSC showed a remarkably increased intracellular killing of MRSA than BMDM. Western blotting revealed the increased level of inflammasome and inflammasome-associated proteins (NLRP3, NLRP6 and ASC) in MRSA infected LMSC. Conclusions These findings have solidified the potential of LMSC-based therapies for pneumonia caused by MRSA and CRKP. However, in vivo (animal) studies are required to determine the effectiveness of LMSC in the clearance of these bacteria and modulation of innate immune responses in the host.