The systemic administration of multipotent mesenchymal stromal cells alters the inflammatory response in the lung during murine polymicrobial sepsis.
5 affiliations
- 1Department of Trauma and Orthopedic Surgery, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
- 2Department of Traumatology, Hand, Plastic and Reconstructive Surgery, Center of Surgery, University of Ulm, Ulm, Germany.
- 3Department of Trauma and Orthopedic Surgery, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. [email protected].
- 4Institute for Transfusion Medicine, University Medical Center Ulm, Ulm, Germany.
- 5Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Donation Service, Ulm, Germany.
Abstract
Sepsis is a life-threatening organ dysfunction and a major cause of acute respiratory distress syndrome (ARDS). Mesenchymal stromal cells (MSCs) have emerged as a potential immunomodulatory therapy, yet preclinical data remain inconsistent. This study investigated the early effects of human MSCs derived from different tissue sources-bone marrow (BMMSCs) and adipose tissue (ASCs)-on systemic and pulmonary inflammation in a murine model of polymicrobial sepsis. 60 male C57BL/6 mice underwent sham treatment, cecal ligation and puncture (CLP), or CLP followed by a single intravenous administration of BMMSCs or ASCs, manufactured according to GMP-compliant protocols. Analyses were performed 8, 24, and 72 h after CLP. Systemic inflammatory mediators were quantified by multiplex analysis, while pulmonary inflammation was assessed by mRNA and protein expression, histology, and immunofluorescence. CLP induced elevated systemic levels of pro-inflammatory mediators, which were not significantly reduced by MSC treatment. In lung tissue, however, MSC administration resulted in selective immunomodulatory effects. Expression of NLR family pyrin domain containing 3 (Nlrp3) was reduced in both MSC-treated groups, while ASC treatment additionally decreased pulmonary interleukin 6 (Il6) and complement 3a receptor (C3ar) mRNA expression at early time points. Protein levels of IL-1β, IL-6, and TNF-α were not significantly altered, although NLRP3 protein expression was reduced following ASC treatment. No significant differences in histological lung injury scores were observed between groups. In summary, MSC treatment induced modest, time-dependent attenuation of pulmonary inflammatory responses in polymicrobial sepsis without improving structural lung injury. No significant differences in pulmonary inflammatory gene expression, protein levels, or histological lung injury scores were observed between BMMSC- and ASC-treated groups, indicating that neither source demonstrated a clear immunomodulatory advantage over the other at the molecular endpoints assessed in this model.
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BibTeX
@article{kanewska2026systemic,
title = {{The systemic administration of multipotent mesenchymal stromal cells alters the inflammatory response in the lung during murine polymicrobial sepsis.}},
author = {Anna Kanewska and Ina Lackner and Marco Dechant and Anne Friedrich and Martina Herrmann and Markus Rojewski and Mario Perl and Jochen Preßmar and Hubert Schrezenmeier and Miriam Kalbitz},
journal = {Cell and tissue research},
year = {2026},
month = oct,
doi = {10.1007/s00441-026-04102-4},
url = {https://europepmc.org/article/MED/42963429},
note = {CC BY},
}
RIS
TY - JOUR
TI - The systemic administration of multipotent mesenchymal stromal cells alters the inflammatory response in the lung during murine polymicrobial sepsis.
AU - Anna Kanewska
AU - Ina Lackner
AU - Marco Dechant
AU - Anne Friedrich
AU - Martina Herrmann
AU - Markus Rojewski
AU - Mario Perl
AU - Jochen Preßmar
AU - Hubert Schrezenmeier
AU - Miriam Kalbitz
PY - 2026
DA - 2026/10/31
JO - Cell and tissue research
DO - 10.1007/s00441-026-04102-4
UR - https://europepmc.org/article/MED/42963429
AB - Sepsis is a life-threatening organ dysfunction and a major cause of acute respiratory distress syndrome (ARDS). Mesenchymal stromal cells (MSCs) have emerged as a potential immunomodulatory therapy, yet preclinical data remain inconsistent. This study investigated the early effects of human MSCs derived from different tissue sources-bone marrow (BMMSCs) and adipose tissue (ASCs)-on systemic and pulmonary inflammation in a murine model of polymicrobial sepsis. 60 male C57BL/6 mice underwent sham treatment, cecal ligation and puncture (CLP), or CLP followed by a single intravenous administration of BMMSCs or ASCs, manufactured according to GMP-compliant protocols. Analyses were performed 8, 24, and 72 h after CLP. Systemic inflammatory mediators were quantified by multiplex analysis, while pulmonary inflammation was assessed by mRNA and protein expression, histology, and immunofluorescence. CLP induced elevated systemic levels of pro-inflammatory mediators, which were not significantly reduced by MSC treatment. In lung tissue, however, MSC administration resulted in selective immunomodulatory effects. Expression of NLR family pyrin domain containing 3 (Nlrp3) was reduced in both MSC-treated groups, while ASC treatment additionally decreased pulmonary interleukin 6 (Il6) and complement 3a receptor (C3ar) mRNA expression at early time points. Protein levels of IL-1β, IL-6, and TNF-α were not significantly altered, although NLRP3 protein expression was reduced following ASC treatment. No significant differences in histological lung injury scores were observed between groups. In summary, MSC treatment induced modest, time-dependent attenuation of pulmonary inflammatory responses in polymicrobial sepsis without improving structural lung injury. No significant differences in pulmonary inflammatory gene expression, protein levels, or histological lung injury scores were observed between BMMSC- and ASC-treated groups, indicating that neither source demonstrated a clear immunomodulatory advantage over the other at the molecular endpoints assessed in this model.
SN - 0302-766X
SN - 1432-0878
ER -