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Human Adipose-Derived Mesenchymal Stem Cells Modify Lung Immunity and Improve Antibacterial Defense in Pneumosepsis Caused by Klebsiella pneumoniae.
Stem Cells Transl Med 2019; 8(8):785-796SC

Abstract

Adult mesenchymal stem cells exert immunomodulatory effects that might improve the host response during sepsis. Knowledge on the effect of adipose-derived mesenchymal stem cells (ASCs) in sepsis is limited. Klebsiella (K.) pneumoniae is a common cause of gram-negative pneumonia and sepsis. This study sought to determine the effect of human ASCs on the host response during pneumosepsis in mice. Mice were infected with K. pneumoniae via the airways to induce a gradually evolving infection in the lung culminating pneumosepsis. One or 6 hours after infection, mice were infused intravenously with ASCs or vehicle, and euthanized after 16 hours or 48 hours, respectively. The effects of freshly cultured and cryopreserved ASCs were compared, the latter formulation being more clinically relevant. Intravenously administered ASCs were visualized in lung tissue by immunostaining at 1 and 3 hours, but not at 15 hours after infusion. Although early after infection, ASCs did not or only modestly influence bacterial loads, they reduced bacterial burdens in lungs and distant organs at 48 hours. ASCs reduced the lung levels of pro-inflammatory cytokines and attenuated lung pathology, but did not influence distant organ injury. ASCs strongly modified the lung transcriptome in uninfected mice and especially mice with pneumosepsis. Cryopreserved and cultured ASCs induced largely similar effects on the lung transcriptome. These data indicate that human ASCs induce profound immune modulatory effects in the lungs, resulting in reduced bacterial burdens and lung inflammation during pneumosepsis caused by a common human pathogen, suggesting that ASCs may be an adjunctive therapeutic in this condition. Stem Cells Translational Medicine 2019;8:785&796.

Authors+Show Affiliations

Center of Experimental & Molecular Medicine, University of Amsterdam, Amsterdam, The Netherlands.Center of Experimental & Molecular Medicine, University of Amsterdam, Amsterdam, The Netherlands.Center of Experimental & Molecular Medicine, University of Amsterdam, Amsterdam, The Netherlands. Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, University of Amsterdam, Amsterdam, The Netherlands.TiGenix SAU, Madrid, Spain.TiGenix SAU, Madrid, Spain.TiGenix NV, Leuven, Belgium.Cologne Center for Genomics (CCG), University of Cologne, Cologne, Germany. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.TiGenix SAU, Madrid, Spain.Center of Experimental & Molecular Medicine, University of Amsterdam, Amsterdam, The Netherlands. Division of Infectious Diseases, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31033196

Citation

Perlee, Desiree, et al. "Human Adipose-Derived Mesenchymal Stem Cells Modify Lung Immunity and Improve Antibacterial Defense in Pneumosepsis Caused By Klebsiella Pneumoniae." Stem Cells Translational Medicine, vol. 8, no. 8, 2019, pp. 785-796.
Perlee D, de Vos AF, Scicluna BP, et al. Human Adipose-Derived Mesenchymal Stem Cells Modify Lung Immunity and Improve Antibacterial Defense in Pneumosepsis Caused by Klebsiella pneumoniae. Stem Cells Transl Med. 2019;8(8):785-796.
Perlee, D., de Vos, A. F., Scicluna, B. P., Mancheño, P., de la Rosa, O., Dalemans, W., ... van der Poll, T. (2019). Human Adipose-Derived Mesenchymal Stem Cells Modify Lung Immunity and Improve Antibacterial Defense in Pneumosepsis Caused by Klebsiella pneumoniae. Stem Cells Translational Medicine, 8(8), pp. 785-796. doi:10.1002/sctm.18-0260.
Perlee D, et al. Human Adipose-Derived Mesenchymal Stem Cells Modify Lung Immunity and Improve Antibacterial Defense in Pneumosepsis Caused By Klebsiella Pneumoniae. Stem Cells Transl Med. 2019;8(8):785-796. PubMed PMID: 31033196.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human Adipose-Derived Mesenchymal Stem Cells Modify Lung Immunity and Improve Antibacterial Defense in Pneumosepsis Caused by Klebsiella pneumoniae. AU - Perlee,Desiree, AU - de Vos,Alex F, AU - Scicluna,Brendon P, AU - Mancheño,Pablo, AU - de la Rosa,Olga, AU - Dalemans,Wilfried, AU - Nürnberg,Peter, AU - Lombardo,Eleuterio, AU - van der Poll,Tom, Y1 - 2019/04/29/ PY - 2018/11/09/received PY - 2019/03/14/accepted PY - 2019/4/30/pubmed PY - 2019/4/30/medline PY - 2019/4/30/entrez KW - Immunomodulation KW - Mesenchymal stem cells KW - Pneumonia KW - Sepsis SP - 785 EP - 796 JF - Stem cells translational medicine JO - Stem Cells Transl Med VL - 8 IS - 8 N2 - Adult mesenchymal stem cells exert immunomodulatory effects that might improve the host response during sepsis. Knowledge on the effect of adipose-derived mesenchymal stem cells (ASCs) in sepsis is limited. Klebsiella (K.) pneumoniae is a common cause of gram-negative pneumonia and sepsis. This study sought to determine the effect of human ASCs on the host response during pneumosepsis in mice. Mice were infected with K. pneumoniae via the airways to induce a gradually evolving infection in the lung culminating pneumosepsis. One or 6 hours after infection, mice were infused intravenously with ASCs or vehicle, and euthanized after 16 hours or 48 hours, respectively. The effects of freshly cultured and cryopreserved ASCs were compared, the latter formulation being more clinically relevant. Intravenously administered ASCs were visualized in lung tissue by immunostaining at 1 and 3 hours, but not at 15 hours after infusion. Although early after infection, ASCs did not or only modestly influence bacterial loads, they reduced bacterial burdens in lungs and distant organs at 48 hours. ASCs reduced the lung levels of pro-inflammatory cytokines and attenuated lung pathology, but did not influence distant organ injury. ASCs strongly modified the lung transcriptome in uninfected mice and especially mice with pneumosepsis. Cryopreserved and cultured ASCs induced largely similar effects on the lung transcriptome. These data indicate that human ASCs induce profound immune modulatory effects in the lungs, resulting in reduced bacterial burdens and lung inflammation during pneumosepsis caused by a common human pathogen, suggesting that ASCs may be an adjunctive therapeutic in this condition. Stem Cells Translational Medicine 2019;8:785&796. SN - 2157-6580 UR - https://www.unboundmedicine.com/medline/citation/31033196/Human_Adipose_Derived_Mesenchymal_Stem_Cells_Modify_Lung_Immunity_and_Improve_Antibacterial_Defense_in_Pneumosepsis_Caused_by_Klebsiella_pneumoniae_ L2 - https://doi.org/10.1002/sctm.18-0260 DB - PRIME DP - Unbound Medicine ER -