Universität zu Köln

Perlee, Desiree, de Vos, Alex F., Scicluna, Brendon P., Mancheno, Pablo, De la Rosa, Olga, Dalemans, Wilfried, Nuernberg, Peter, Lombardo, Eleuterio and Van der Poll, Tom (2019). Human Adipose-Derived Mesenchymal Stem Cells Modify Lung Immunity and Improve Antibacterial Defense in Pneumosepsis Caused by Klebsiella pneumoniae. Stem Cells Transl. Med., 8 (8). S. 785 - 797. HOBOKEN: WILEY. ISSN 2157-6580

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Perlee, Desiree UNSPECIFIED UNSPECIFIED UNSPECIFIED de Vos, Alex F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Scicluna, Brendon P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mancheno, Pablo UNSPECIFIED UNSPECIFIED UNSPECIFIED De la Rosa, Olga UNSPECIFIED UNSPECIFIED UNSPECIFIED Dalemans, Wilfried UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Lombardo, Eleuterio UNSPECIFIED UNSPECIFIED UNSPECIFIED Van der Poll, Tom UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-133930
DOI:	10.1002/sctm.18-0260
Journal or Publication Title:	Stem Cells Transl. Med.
Volume:	8
Number:	8
Page Range:	S. 785 - 797
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	2157-6580
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COMMUNITY-ACQUIRED PNEUMONIA; ACUTE RESPIRATORY-DISTRESS; UMBILICAL-CORD BLOOD; STROMAL CELLS; BONE-MARROW; EXPERIMENTAL COLITIS; BACTERIAL CLEARANCE; PULMONARY INFECTION; SEPSIS; INJURY Multiple languages Cell & Tissue Engineering Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13393