Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Inflammation Research
Published in: Inflammation Research 9/2014

01-09-2014 | Original Research Paper

Mesenchymal stem cells decrease splenocytes apoptosis in a sepsis experimental model

Authors: Leonardo Pedrazza, Adroaldo Lunardelli, Carolina Luft, Carolina Uribe Cruz, Fernanda Cristina de Mesquita, Shanna Bitencourt, Fernanda Bordignon Nunes, Jarbas Rodrigues de Oliveira

Published in: Inflammation Research | Issue 9/2014

Login to get access

Abstract

Objective and design

Mesenchymal stem cells (MSCs) are potent modulators of immune responses. Sepsis is the association of a systemic inflammatory response with an infection. The aim of this study was to test the ability of MSCs derived from adipose tissue, which have immunomodulatory effects, and to inhibit the septic process in an experimental model of mice.

Methods

Three experimental groups (male C57BL/6 mice) were formed for the test: control group, untreated septic group and septic group treated with MSCs (1 × 106 cells/animal).

Results

In the control group, there were no deaths; in the untreated septic group, the mortality rate was 100 % within 26 h; in the septic group treated with MSCs, the mortality rate reached 40 % within 26 h. The group treated with MSCs was able to reduce the markers of tissue damage in the liver and pancreas. The treated group had a reduction of inflammatory markers. Furthermore, the MSCs-treated group was able to inhibit the increase of apoptosis in splenocytes observed in the untreated septic group.

Conclusions

Our data showed that MSCs ameliorated the immune response with decrease of inflammatory cytokines and increase anti-inflammatory IL-10; moreover, inhibited splenocytes apoptosis and, consequently, inhibited tissue damage during sepsis.
Literature
1.
Angus DC, Linde-Zwirble WT, Lidicker JMA, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–10.PubMedCrossRef
2.
Nguyen HB, Rivers EP, Abrahamian FM, Moran GJ, Abraham E, Trzeciak S, Huang DT, Osborn T, Stevens D, Talan DA. Severe sepsis and septic shock: review of the literature and emergency department management guidelines. Ann Emerg Med. 2006;48:28–54.PubMed
3.
Hotchkiss RS, Nicholson DW. Apoptosis and caspases regulate death and inflammation in sepsis. Nature. 2006;6:813–22.
4.
Oberholzer A, Oberholzer C, Moldawer LL. Sepsis syndromes: understanding the role of innate and acquired immunity. Shock. 2001;16:83–96.PubMedCrossRef
5.
Huttunen R, Aittoniemi J. New concepts in the pathogenesis, diagnosis and treatment of bacteremia and sepsis. J Infect. 2011;63:407–19.PubMedCrossRef
6.
7.
Wannemuehler TJ, Manukyan MC, Brewster BD, Rouch J, Poynter JA, Wang Y, Meldrum DR. Advances in mesenchymal stem cell research in sepsis. J Surg Res. 2011;173:113–26.PubMedCrossRef
8.
Gerlach H, Toussaint S. Managing septic shock. F1000 Medicine Reports 2010;2:40.
9.
Barry FP, Murphy JM. Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol. 2004;36:568–84.PubMedCrossRef
10.
Baksh D, Song L, Tuan RS. Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med. 2004;8:301–16.PubMedCrossRef
11.
Wang M, Crisostomo PR, Herring C, Meldrum KK, Meldrum DR. Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF and IGF-1 in response to TNF by a p38 mitogen activated protein kinase dependent mechanism. Am J Physiol Regul Integr Comp Physiol. 2006;291:880–4.CrossRef
12.
Weil BR, Manukyan MC, Herrmann JL, Wang Y, Abarbanell AM, Poynter JA, Meldrum DR. Mesenchymal stem cells attenuate myocardial functional depression and reduce systemic and myocardial inflammation during endotoxemia. Surgery. 2010;148:444–52.PubMedCrossRef
13.
Mei SHJ, McCarter SD, Deng Y, Parker CH, Liles WC, Stewart DJ. Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing Angiopoietin 1. PLoS Med. 2007;4:1525–37.CrossRef
14.
Soleymaninejadia E, Pramanik K, Samadian E. Immunomodulatory properties of mesenchymal stem cells: cytokines and factors. Am J Reprod Immunol. 2012;67:1–8.CrossRef
15.
16.
van Poll D, Parekkadan B, Cho CH, Berthiaume F, Nahmias Y, Tilles AW, Yarmush ML. Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo. Hepatology. 2008;47:1634–43.PubMedCrossRef
17.
Németh K, Leelahavanichkul A, Yuen PST, Mayer B, Parmelee A, Doi K, Robey PG, Leelahavanichkul K, Koller BH, Brown JM, Hu X, Jelinek I, Star RA, Mezey E. Bone marrow stromal cells attenuate sepsis via prostaglandin E2-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med. 2009;15:42–9.PubMedCentralPubMedCrossRef
18.
Krasnodembskaya A, Samarani G, Song Y, Zhuo H, Su X, Lee JW, Gupta N, Petrini M, Matthay MA. Human mesenchymal stem cells reduce mortality and bacteremia in gram negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes. Am J Physiol Lung Cell Mol Physiol. 2012;302:1003–13.
19.
Mosna F, Sensebé L, Krampera M. Human bone marrow and adipose tissue mesenchymal stem cells: a user’s guide. Stem Cells Dev. 2010;19(10):1449–70.PubMedCrossRef
20.
Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7:211–28.PubMedCrossRef
21.
Nunes FB, Pires MGS, Filho JCFA, Wächter PH, Oliveira JR. Physiopathological studies in septic rats and the use of fructose-1,6-bisphosphate as cellular protection. Crit Care Med. 2002;30(9):2069–74.PubMedCrossRef
22.
Schulz SM, Köhler G, Holscher C, Iwakura Y, Alber G. IL-17A is produced by Th17, gammadelta T cells and other CD42 lymphocytes during infection with Salmonella enterica serovar Enteritidis and has a mild effect in bacterial clearance. Int Immunol. 2008;20:1129–38.PubMedCrossRef
23.
Ellger B, Debaveye Y, Vanhorebeek I, Langouche L, Giulietti A, Van Etten E, Herijgers P, Mathieu C, Van den Berghe G. Survival benefits of intensive insulin therapy in critical illness: impact of maintaining normoglycemia versus glycemia-independent actions of insulin. Diabetes. 2006;55:1096–105.PubMedCrossRef
24.
Branco RG, Tasker RC, Ramos Garcia PC, Piva JP, Dias Xavier L. Glycemic control and insulin therapy in sepsis and critical illness. J Pediatr. 2007;83:128–36.CrossRef
25.
Mizock BA. Alterations in fuel metabolism in critical illness: hyperglycaemia. Best Pract Res Clin Endocrinol Metab. 2001;15:533–51.PubMedCrossRef
26.
Yagi H, Soto-Gutierrez A, Parekkadan B, Kitagawa Y, Tompkins RG, Kobayashi N, Yarmush ML. Mesenchymal stem cells: mechanisms of immunomodulation and homing. Cell Transpl. 2010;19:667–79.CrossRef
27.
Mizuno H. Adipose-derived stem cells for tissue repair and regeneration: ten years of research and a literature review. J Nippon Med Sch. 2009;76:56–66.PubMedCrossRef
28.
Askari AT, Unzek S, Popovic ZB, Goldman CK, Forudi F, Kiedrowski M, Rovner A, Ellis SG, Thomas JD, DiCorleto PE, Topol EJ, Penn MS. Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet. 2003;362:697–703.PubMedCrossRef
29.
Rojas M, Xu J, Woods CR, Mora AL, Spears W, Roman J, Brigham KL. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol. 2005;33:145–52.PubMedCentralPubMedCrossRef
30.
Hoogduijn MJ, Popp F, Verbeek R, Masoodi M, Nicolaou A, Baan C, Dahlke MH. The immunomodulatory properties of mesenchymal stem cells and their use for immunotherapy. Int Immunopharmacol. 2010;10:1496–500.PubMedCrossRef
31.
Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, Zhao RC, Shi Y. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2008;2:141–50.PubMedCrossRef
32.
Muenzer JT, Davis CG, Chang K, Schmidt RE, Dunne WM, Coopersmith CM, Hotchkiss RS. Characterization and modulation of the immunosuppressive phase of sepsis. Infect Immun. 2010;78:1582–92.PubMedCentralPubMedCrossRef
33.
Qiu P, Cui X, Barochia A, Li Y, Natanson C, Eichacker PQ. The evolving experience with therapeutic TNF inhibition in sepsis: considering the potential influence of risk of death. Expert Opin Investig Drugs. 2011;20:1555–64.PubMedCentralPubMedCrossRef
34.
Webb S. The role of mediators in sepsis resolution. Adv Sepsis. 2002;2:8–14.
35.
Gomes RN, Figueiredo RT, Bozza FA, Pacheco P, Amâncio RT, Laranjeira AP, Castro-Faria-Neto HC, Bozza PT, Bozza MT. Increased susceptibility to septic and endotoxic shock in monocyte chemoattractant protein 1/CC chemokine ligand 2-deficient mice correlates with reduced interleukin 10 and enhanced macrophage migration inhibitory factor production. Shock. 2006;26:457–63.PubMedCrossRef
36.
Matsukawa A, Hogaboam CM, Lukacs NW, Lincoln PM, Strieter RM, Kunkel SL. Endogenous monocyte chemoattractant protein-1 (MCP-1) protects mice in a model of acute septic peritonitis: cross-talk between MCP-1 and leukotriene B4. J Immunol. 1999;163:6148–54.PubMed
37.
Matsukawa A, Hogaboam CM, Lukacs NW, Lincoln PM, Strieter RM, Kunkel SL. Endogenous MCP-1 influences systemic cytokine balance in a murine model of acute septic peritonitis. Exp Mol Pathol. 2000;68:77–84.PubMedCrossRef
38.
Bossink AWJ, Paemen L, Jansen PM, Hack CE, Thijs LG, Van Damme J. Plasma levels of the chemokines monocyte chemotactic proteins-1 and -2 are elevated in human sepsis. Blood. 1995;86:3841–7.PubMed
39.
Bozza FA, Salluh JI, Japiassu AM, Soares M, Assis EF, Gomes RN, Bozza MT, Castro-Faria-Neto HC, Bozza PT. Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit Care. 2007;11:R49.PubMedCentralPubMedCrossRef
40.
Speyer CL, Gao H, Rancilio NJ, Neff TA, Huffnagle GB, Sarma JV, Ward PA. Novel chemokine responsiveness and mobilization of neutrophils during sepsis. Am J Pathol. 2004;165:2187–96.PubMedCentralPubMedCrossRef
41.
Gonzalez-Rey E, Anderson P, González MA, Rico L, Büscher D, Delgado M. Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis. Gut. 2009;58:929–39.PubMedCrossRef
42.
Monneret G. How to identify systemic sepsis-induced immunoparalysis. Adv Sepsis. 2005;4:42–9.
43.
Hotchkiss RS, Tinsley KW, Swanson PE, Schmieg RE Jr, Hui JJ, Chang KC, Osborne DF, Freeman BD, Cobb JP, Buchman TG, Karl IE. Sepsis-induced apoptosis causes progressive profound depletion of B and CD4 + T lymphocytes in humans. J Immunol. 2001;166:6952–63.PubMedCrossRef
44.
Le Tulzo Y, Pangault C, Gacouin A, Guilloux V, Tribut O, Amiot L, Tattevin P, Thomas R, Fauchet R, Drénou B. Early circulating lymphocyte apoptosis in human septic shock is associated with poor outcome. Shock. 2002;18:487–94.PubMedCrossRef
45.
Hotchkiss RS, Chang KC, Grayson MH, Tinsley KW, Dunne BS, Davis CG, Osborne DF, Karl IE. Adoptive transfer of apoptotic splenocytes worsens survival, whereas adoptive transfer of necrotic splenocytes improves survival in sepsis. PNAS. 2003;100:6724–9.PubMedCentralPubMedCrossRef
Metadata
Title
Mesenchymal stem cells decrease splenocytes apoptosis in a sepsis experimental model
Authors
Leonardo Pedrazza
Adroaldo Lunardelli
Carolina Luft
Carolina Uribe Cruz
Fernanda Cristina de Mesquita
Shanna Bitencourt
Fernanda Bordignon Nunes
Jarbas Rodrigues de Oliveira
Publication date
01-09-2014
Publisher
Springer Basel
Published in
Inflammation Research / Issue 9/2014
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-014-0745-1

Other articles of this Issue 9/2014

Inflammation Research 9/2014 Go to the issue

Original Research Paper

Intravenous immunoglobulin preparation prevents the production of pro-inflammatory cytokines by modulating NFκB and MAPKs pathways in the human monocytic THP-1 cells stimulated with procalcitonin

Letter to the Editor

IL-18 promoter polymorphisms under scrutiny

Original Research Paper

Fisetin inhibits high-glucose-induced vascular inflammation in vitro and in vivo

Original Research Paper

Role of main neuroendocrine pathways activated by swim stress on mast cell-dependent peritoneal TNF production after LPS administration in mice

Original Research Paper

Water-soluble phenol TS-13 combats acute but not chronic inflammation

Original Research Paper

Soluble biglycan induces the production of ICAM-1 and MCP-1 in human aortic valve interstitial cells through TLR2/4 and the ERK1/2 pathway
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits