The 5-lipoxygenase pathway regulates vasculogenesis in differentiating mouse embryonic stem cells

Finkensieper, Andreas; Kieser, Sophia; Bekhite, Mohamed M.; Richter, Madeleine; Mueller, Joerg P.; Graebner, Rolf; Figulla, Hans‐Reiner; Sauer, Heinrich; Wartenberg, Maria

doi:10.1093/cvr/cvp385

Cited by 18 publications

(16 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2). EBs of day 18 were chosen, because it was previously described in the literature that leukocytes and macrophages were definitely detectable after day 12 of differentiation within the murine ES cell lines [11,19]. Interestingly, a significant reduction of E. coli CFUs was found in the presence of differentiated 18-day-old CGR8 EBs in comparison to E. coli culture without coincubation ( Fig.…”

Section: Es Cell-derived Ebs Differentiate Into Cells Of the Innate Imentioning

confidence: 74%

Antibacterial Capacity of Differentiated Murine Embryonic Stem Cells During Defined In Vitro Inflammatory Conditions

Finkensieper

Bekhite

Fischer

et al. 2013

Stem Cells and Development

Self Cite

View full text Add to dashboard Cite

Embryonic stem (ES) cells are a powerful model for the development of cells responsible for the cellular immune response. Therefore, we analyzed the defense and phagocytic capacity of embryoid bodies (EBs) derived from ES cells using in the vitro inflammatory conditions caused by Escherichia coli. Further, we used this phagocytic activity to purify activated immune cells. Our data show that spontaneously differentiated 18-day-old EBs of the cell line CGR8 contained immune cells, which were positive for CD45, CD68, CD11b, F4/80, and CD19. Exposure of these EBs to E. coli with defined infection doses of bacterial colony-forming units (CFUs) led to a significant time-dependent reduction of CFUs, indicating the immune responses exerted by EBs. This was paralleled by an upregulation of inflammatory cytokines, that is, IL-1β and TNF-α. Western blot analysis of infected EBs indicated an upregulation of CD14 and cytochrome b-245 heavy chain (NOX2). Silencing of NOX2 significantly reduced the antibacterial capacity of EBs, which was partially explained by reduction of F4/80-positive cells. To identify, isolate, and further cultivate phagocytic active cells from differentiated EBs, a cocultivation assay of differentiated ES cells with green fluorescent protein (GFP)-labeled E. coli was established. Colocalization of GFP-labeled E. coli with cells positive for CD45, CD68, and F4/80 revealed time-dependent phagocytotic uptake, which was underlined by colocalization with the LysoTracker-Red(®) dye as well as preincubation with cytochalasin D. In conclusion, a primitive immune response with efficient phagocytosis was responsible for the antibacterial capacity of differentiated EBs.

show abstract

Section: Es Cell-derived Ebs Differentiate Into Cells Of the Innate Imentioning

confidence: 74%

Antibacterial Capacity of Differentiated Murine Embryonic Stem Cells During Defined In Vitro Inflammatory Conditions

Finkensieper

Bekhite

Fischer

et al. 2013

Stem Cells and Development

Self Cite

View full text Add to dashboard Cite

show abstract

“…Within the 3-dimensional tissue of embryoid bodies blood vessel-like structures are formed and -most importantly -leukocytes are differentiated [Finkensieper et al, 2010;Sharifpanah et al, 2015]. These immune-competent cells may be critically involved in the inflamma- tory and cellular immune response towards the biomaterial.…”

Section: Discussionmentioning

confidence: 99%

Embryonic Stem Cells for Tissue Biocompatibility, Angiogenesis, and Inflammation Testing

Sharifpanah

Reinhardt²,

Schönleben³

et al. 2017

Cells Tissues Organs

Self Cite

View full text Add to dashboard Cite

Aim: To introduce embryoid bodies derived from mouse embryonic stem (ES) cells, which differentiate blood vessel-like structures and leukocytes, as a novel in vitro model system for biocompatibility, inflammation, and angiogenesis studies. Methodology/Results: Punched spherical discs of bioabsorbable polymers (ε-caprolactone and L-lactide in different compositions) with a diameter of 2 mm and a thickness of 0.2 mm were inoculated with embryoid bodies for cocultivation. As reference material for biocompatible, nonbioabsorbable, and bioincompatible materials, polymer punched discs of petriPERM (PP) membrane (polytetrafluoroethylene) as well as polyvinylchloride (PVC) were used. Tissue outgrowth on the polymer discs decreased and cell toxicity increased upon confrontation on bioabsorbable biomaterials and PVC. Bioabsorbable polymers as well as PVC decreased the branching points and total tube length of CD31-positive vascular structures in embryoid bodies. With the exception of PP, all applied materials increased the differentiation of CD68-positive macrophages and the generation of reactive oxygen species, which is indicative of proinflammatory processes upon contact of tissue with biomaterials. Consequently, cocultivation with polymers increased secretion of the cytokines interleukin-6, monocyte chemotactic protein-1, and tumor necrosis factor-α. Conclusion: Three-dimensional tissues cultivated from ES cells are well-suited for testing the biocompatibility, the vascular response, and the inflammatory reaction towards bioabsorbable and nonbioabsorbable polymers.

show abstract

“…Similar to PGE, leukotrienes and lipoxins also influence myelopoiesis, proliferation of granulocyte-macrophage progenitors, and vasculogenesis by acting on differentiating mouse embryonic stem cells, neural stem cell proliferation and regulate growth and differentiation of rat myoblasts via the BLT1 pathway [81][82][83][84][85][86][87][88]. Thromboxane A 2 , a product of AA metabolism, appears to play a key role in the migration, proliferation, and differentiation of human adipose tissuederived mesenchymal stem cells into smooth muscle-like cells through signaling mechanisms involving ERK and p38 MAPK [89].…”

Section: Efas/pufas and Their Metabolites In Stem Cell Proliferation mentioning

confidence: 99%

Essential fatty acids and their metabolites as modulators of stem cell biology with reference to inflammation, cancer, and metastasis

Das

2011

Cancer Metastasis Rev

View full text Add to dashboard Cite

Stem cells are pluripotent and expected to be of benefit in the management of coronary heart disease, stroke, diabetes mellitus, cancer, and Alzheimer's disease in which pro-inflammatory cytokines are increased. Identifying endogenous bioactive molecules that have a regulatory role in stem cell survival, proliferation, and differentiation may aid in the use of stem cells in various diseases including cancer. Essential fatty acids form precursors to both pro- and anti-inflammatory molecules have been shown to regulate gene expression, enzyme activity, modulate inflammation and immune response, gluconeogenesis via direct and indirect pathways, function directly as agonists of a number of G protein-coupled receptors, activate phosphatidylinositol 3-kinase/Akt and p44/42 mitogen-activated protein kinases, and stimulate cell proliferation via Ca(2+), phospholipase C/protein kinase, events that are also necessary for stem cell survival, proliferation, and differentiation. Hence, it is likely that bioactive lipids play a significant role in various diseases by modulating the proliferation and differentiation of embryonic stem cells in addition to their capacity to suppress inflammation. Ephrin Bs and reelin, adhesion molecules, and microRNAs regulate neuronal migration and cancer cell metastasis. Polyunsaturated fatty acids and their products seem to modulate the expression of ephrin Bs and reelin and several adhesion molecules and microRNAs suggesting that bioactive lipids participate in neuronal regeneration and stem cell proliferation, migration, and cancer cell metastasis. Thus, there appears to be a close interaction among essential fatty acids, their bioactive products, and inflammation and cancer growth and its metastasis.

show abstract

The 5-lipoxygenase pathway regulates vasculogenesis in differentiating mouse embryonic stem cells

Abstract: Our data demonstrate that the 5-LO pathway emerges early during ES cell differentiation into cells of the myeloid lineage and that LTs play an until now unrecognized role in vascular development of ES cells.

Cited by 18 publications

References 35 publications

Antibacterial Capacity of Differentiated Murine Embryonic Stem Cells During Defined In Vitro Inflammatory Conditions

Antibacterial Capacity of Differentiated Murine Embryonic Stem Cells During Defined In Vitro Inflammatory Conditions

Embryonic Stem Cells for Tissue Biocompatibility, Angiogenesis, and Inflammation Testing

Essential fatty acids and their metabolites as modulators of stem cell biology with reference to inflammation, cancer, and metastasis

Contact Info

Product

Resources

About