Host Defense against Pneumonia Is Augmented by Lung-Derived Mesenchymal Stem Cells

Authors

Tirumalai Rangasamy, Center for Lung Biology and Disease, Louisiana State University, Baton Rouge, LA; jey@lsu.edu trangasamy@lsu.edu.
Laxman Ghimire, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA; and.
Liliang Jin, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA; and.
John Le, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA; and.
Sivakumar Periasamy, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA; and.
Sagar Paudel, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA; and.
Shanshan Cai, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA; and.
Samithamby Jeyaseelan, Center for Lung Biology and Disease, Louisiana State University, Baton Rouge, LA; jey@lsu.edu trangasamy@lsu.edu.

Document Type

Article

Publication Date

8-15-2021

Abstract

is a common cause of Gram-negative pneumonia. The spread of antibiotic-resistant and hypervirulent strains has made treatment more challenging. This study sought to determine the immunomodulatory, antibacterial, and therapeutic potential of purified murine stem cell Ag-1 (Sca-1) lung mesenchymal stem cells (LMSCs) using in vitro cell culture and an in vivo mouse model of pneumonia caused by Sca-1 LMSCs are plastic adherent, possess colony-forming capacity, express mesenchymal stem cell markers, differentiate into osteogenic and adipogenic lineages in vitro, and exhibit a high proliferative capacity. Further, these Sca-1 LMSCs are morphologically similar to fibroblasts but differ ultrastructurally. Moreover, Sca-1 LMSCs have the capacity to inhibit LPS-induced secretion of inflammatory cytokines by bone marrow-derived macrophages and neutrophils in vitro. Sca-1 LMSCs inhibit the growth of more potently than do neutrophils. Sca-1 LMSCs also possess the intrinsic ability to phagocytize and kill intracellularly. Whereas the induction of autophagy promotes bacterial replication, inhibition of autophagy enhances the intracellular clearance of in Sca-1 LMSCs during the early time of infection. Adoptive transfer of Sca-1 LMSCs in -infected mice improved survival, reduced inflammatory cells in bronchoalveolar lavage fluid, reduced inflammatory cytokine levels and pathological lesions in the lung, and enhanced bacterial clearance in the lung and in extrapulmonary organs. To our knowledge, these results together illustrate for the first time the protective role of LMSCs in bacterial pneumonia.

Publication Source (Journal or Book title)

Journal of immunology (Baltimore, Md. : 1950)

First Page

1112

Last Page

1127

Recommended Citation

Rangasamy, T., Ghimire, L., Jin, L., Le, J., Periasamy, S., Paudel, S., Cai, S., & Jeyaseelan, S. (2021). Host Defense against Pneumonia Is Augmented by Lung-Derived Mesenchymal Stem Cells. Journal of immunology (Baltimore, Md. : 1950), 207 (4), 1112-1127. https://doi.org/10.4049/jimmunol.2000688