Affiliation:
1. Affiliated Hospital of Yunnan University (The Second People’s Hospital of Yunnan Province), School of Medicine, Yunnan University, Kunming, China
2. Department of Obstetrics, The First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
3. Department of Infectious Diseases, The First People’s Hospital of Fuzhou, Fuzhou, China
4. Institute of Neuroscience, Kunming Medicine University, Kunming, China
5. The Third Clinical School of Medicine, Jinzhou Medical University, Jinzhou, China
Abstract
Bone marrow stromal cells (BMSCs) have emerged as a potential therapy for sepsis, yet the underlying mechanisms remain unclear. In this study, we investigated the effects of BMSCs on serum inflammatory cytokines in a rat model of lipopolysaccharide (LPS)-induced sepsis. Sepsis was induced by intravenous injection of LPS, followed by transplantation of BMSCs. We monitored survival rates for 72 h and evaluated organ functions, histopathological changes, and cytokines expression. Sepsis rats showed decreased levels of white blood cells, platelets, lymphocyte ratio, and oxygen partial pressure, along with increased levels of neutrophil ratio, carbon dioxide partial pressure, lactic acid, alanine aminotransferase, and aspartate aminotransferase. Histologically, lung, intestine, and liver tissues exhibited congestion, edema, and infiltration of inflammatory cells. However, after BMSCs treatment, there was improvement in organ functions, histopathological injuries, and survival rates. Protein microarray analysis revealed significant changes in the expression of 12 out of 34 inflammatory cytokines. These findings were confirmed by enzyme-linked immunosorbent assay. Pro-inflammatory factors, such as interleukin-1β (IL-1β), IL-1α, tumor necrosis factor-α (TNF-α), tissue inhibitor of metal protease 1 (TIMP-1), matrix metalloproteinase 8 (MMP-8), Leptin, and L-selectin were upregulated in sepsis, whereas anti-inflammatory and growth factors, including IL-4, β-nerve growth factor (β-NGF), ciliary neurotrophic factor (CNTF), interferon γ (IFN-γ), and Activin A were downregulated. BMSCs transplantation led to a decrease in pro-inflammatory cytokines and an increase in anti-inflammatory and growth factors. We summarized relevant molecular signaling pathways that resulted from cytokines in BMSCs for treating sepsis. Our results illustrated that BMSCs could promote tissue repair and improve organ functions and survival rates in sepsis through modulating cytokine networks.
Funder
Yunnan Health Training Project of High Level Talents
Yunnan Universities Scientific and Technical Innovation Team
Yunnan Applied Basic Research Project Foundation
National Natural Science Foundation of China
Yunnan University Donglu Talent Young Scholar
Yunnan Province Clinical Research Center for Gynecological and Obstetric Disease
Association Foundation Program of Yunnan Provincial science and Technology Department and Kunming Medicine University
Subject
Transplantation,Cell Biology,Biomedical Engineering
Cited by
1 articles.
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