Immunomodulatory and cardio-protective effects of differentially originated multipotent mesenchymal stroma cells during polymicrobial sepsis in mice

Figures

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  Fig. 1. Elevated plasma levels of Troponin I and Heart-Type Fatty Acid Binding Protein (HFABP) in cecal ligation puncture procedure (CLP) mice in comparison to sham. Wildtype mice received either sham treatment, CLP procedure with or without Bone-marrow derived mesenchymal stem cells (BMMSC) or Adipose Stromal Cells (ASC) therapy. Plasma of 8 h following CLP procedure was used for ELISA analysis. A Plasma Troponin I level in ng/ml. B Plasma HFABP level in ng/ml. Data are presented as mean ± SEM. p ≤ 0.05 was considered as statistically significant. *p ≤ 0.05, sham vs. CLP, sham vs. ASC, sham vs. BMMSC. Each bar N = 5

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  Fig. 2. Morphological changes in all CLP treatment groups in comparison to sham. Wildtype mice received either sham treatment, CLP procedure with or without BMMSC or ACS therapy. Left ventricles 8 h, 24 h or 72 h following CLP procedure were processed into paraffine slides and stained with H.E. A–H Representative images of Hematoxylin Eosin staining of the left ventricle of mice sacrificed after 24 h (A–D) and 72 h (E–H) belonging to treatment groups sham, CLP, BMMSC and ACS with ventricle rupture (B, black arrow), apoptosis (F, black square) and intramuscular bleeding (F, H, black circle). I Comparison of the histology damage scores between the different treatment groups sacrificed after 8 h, 24 h and 72 h. Data are presented as mean ± SEM. p ≤ 0.05 was considered as statistically significant. *p ≤ 0.05, sham vs. CLP, sham vs. ASC, sham vs. BMMSC. Each bar N = 5

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  Fig. 3. Upregulated tumor necrosis factor alpha (Tnfa) gene expression in left ventricle of CLP mice. Wildtype mice received either sham treatment, CLP procedure with or without BMMSC or ACS therapy. Left ventricle was analyzed 8 h, 24 h or 72 h following CLP procedure. A–C mRNA expression of tumor necrosis factor in fold change. Data are presented as mean ± SEM. p ≤ 0.05 was considered as statistically significant. *p ≤ 0.05, ** p ≤ 0.005, CLP vs. sham, CLP vs. BMMSC, CLP vs. ASC. Each bar N = 5

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  Fig. 4. Complement component 3a (C3ar) and complement 5a receptor 1 (C5ar1) upregulation in left ventricle in polymicrobial sepsis. Wildtype mice received either sham treatment, CLP procedure with or without BMMSC or ACS therapy. Left ventricle was analyzed 8 h, 24 h or 72 h after CLP + treatment. A–C Local mRNA expression of C5ar1 in fold change. D–F mRNA expression of C3ar in fold change. G–I Protein expression of C3 alpha chain in protein band intensity. Data are presented as mean ± SEM. p ≤ 0.05 was considered as statistically significant. *p ≤ 0.05, ** p ≤ 0.005, *** p ≤ 0.0005, CLP vs. sham, CLP vs. BMMSC, CLP vs. ASC. Each bar N = 5

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  Fig. 5. Interleukin (Il)−6, Il-1b and Il-10 upregulation in left ventricle of CLP mice. Wildtype mice received either sham treatment, CLP procedure with or without BMMSC or ACS therapy. Left ventricle was analyzed 8 h, 24 h or 72 h following CLP procedure. A–C mRNA expression of Il-1b in fold change. D–F mRNA expression of Il-6 in fold change. G–I mRNA expression of Il-10 in fold change. Data are presented as mean ± SEM. p ≤ 0.05 was considered as statistically significant. *p ≤ 0.05, ** p ≤ 0.005, *** p ≤ 0.0005, CLP vs. sham, CLP vs. BMMSC, CLP vs. ASC. Each bar N = 5

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  Fig. 6. Upregulation of Toll-Like Receptor (Tlr) 2 in left ventricle in polymicrobial sepsis. Wildtype mice received either sham treatment, CLP procedure with or without BMMSC or ACS therapy. Left ventricle was analyzed 8 h, 24 h or 72 h following CLP procedure. A–C mRNA expression of Tlr-2 in fold change. D–F mRNA expression of Tlr-4 in fold change. G–I mRNA expression of Tlr-9 in fold change. Data are presented as mean ± SEM. p ≤ 0.05 was considered as statistically significant. *p ≤ 0.05, ** p ≤ 0.005, *** p ≤ 0.0005, CLP vs. sham, CLP vs. BMMSC, CLP vs. ASC. Each bar N = 5

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  Fig. 7. Upregulated NOD-, LRR- and pyrin domain-containing protein 3 (Nlrp3) expression in left ventricle of CLP mice. Wildtype mice received either sham treatment, CLP procedure with or without BMMSC or ACS therapy. Left ventricle was analyzed 8 h, 24 h or 72 h following CLP procedure. A–C mRNA expression of Nlrp3 inflammasome in fold change and D–F protein expression in protein band intensity. Data are presented as mean ± SEM. p ≤ 0.05 was considered as statistically significant. *p ≤ 0.05, CLP vs. sham, CLP vs. BMMSC, CLP vs. ASC. Each bar N = 5