Cited by 2,364Mesenchymal stem cell researchSepsis Diagnosis and TreatmentImmune cells in cancer

Bone marrow stromal cells attenuate sepsis via prostaglandin E2–dependent reprogramming of host macrophages to increase their interleukin-10 production

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Németh, Krisztián, Leelahavanichkul, Asada, Yuen, Peter S T, Mayer, Balázs, Parmelee, Alissa, Doi, Kent, Robey, Pamela G, Leelahavanichkul, Kantima +6 more·2009·Nature Medicine

Abstract

Sepsis causes over 200,000 deaths yearly in the US; better treatments are urgently needed. Administering bone marrow stromal cells (BMSCs -- also known as mesenchymal stem cells) to mice before or shortly after inducing sepsis by cecal ligation and puncture reduced mortality and improved organ function. The beneficial effect of BMSCs was eliminated by macrophage depletion or pretreatment with antibodies specific for interleukin-10 (IL-10) or IL-10 receptor. Monocytes and/or macrophages from septic lungs made more IL-10 when prepared from mice treated with BMSCs versus untreated mice. Lipopolysaccharide (LPS)-stimulated macrophages produced more IL-10 when cultured with BMSCs, but this effect was eliminated if the BMSCs lacked the genes encoding Toll-like receptor 4, myeloid differentiation primary response gene-88, tumor necrosis factor (TNF) receptor-1a or cyclooxygenase-2. Our results suggest that BMSCs (activated by LPS or TNF-alpha) reprogram macrophages by releasing prostaglandin E(2) that acts on the macrophages through the prostaglandin EP2 and EP4 receptors. Because BMSCs have been successfully given to humans and can easily be cultured and might be used without human leukocyte antigen matching, we suggest that cultured, banked human BMSCs may be effective in treating sepsis in high-risk patient groups.

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Authors
Németh, K., Leelahavanichkul, A., Yuen, P. S. T., Mayer, B., Parmelee, A., Doi, K., Robey, P. G., Leelahavanichkul, K., Koller, B. H., Brown, J. M., Hu, X., Jelinek, I., Star, R. A., & Mezey, É.
Affiliations
  • National Institutes of Health (US)
  • National Institute of Diabetes and Digestive and Kidney Diseases (US)
  • National Institute of Dental and Craniofacial Research (US)
  • University of North Carolina at Chapel Hill (US)
  • East Carolina University (US)
Corresponding author
Mezey, Éva
Venue
Nature Medicine
Published
2008-11-21
Volume
15
Issue
1
Pages
42-49
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W2111727066
Cited by
2,364
References
49
Citations by year
2026: 52 · 2025: 60 · 2024: 82 · 2023: 131 · 2022: 138 · 2021: 167 · 2020: 186 · 2019: 171 · 2018: 176 · 2017: 148 · 2016: 201 · 2015: 167 · 2014: 172 · 2013: 148 · 2012: 144
FWCI
32.25
Type
journal article
Language
en
Update notices
erratum (2009-04-01)
Open access
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • The Scholarship East Carolina University's Institutional Repository (East Carolina University) (submittedVersion)
  • UNC Libraries
Funders
  • National Institutes of Health
  • National Cancer Institute
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • National Institute of Dental and Craniofacial Research (Z01DE000714)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords
sepsis, mesenchymal stem cells, macrophage reprogramming, IL-10, prostaglandin E2, TLR4, MyD88, TNF receptor 1, cyclooxygenase-2, innate immunity, cecal ligation and puncture, immunomodulation
MeSH terms
Animals, Bone Marrow Cells, Cecal Diseases, Cecum, Humans, Macrophages, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Models, Biological, Transplantation, Wounds, Penetrating, Dinoprostone, Survival Analysis, Bone Marrow Transplantation, Interleukin-10, Stromal Cells, Sepsis, Mice, Cellular Reprogramming

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