Impact of bacteria and bacterial components on osteogenic and adipogenic differentiation of adipose-derived mesenchymal stem cells

Fiedler, Tomas; Salamon, Achim; Adam, Stefanie; Herzmann, Nicole; Taubenheim, Jan; Peters, Kirsten

doi:10.1016/j.yexcr.2013.08.020

Cited by 63 publications

(60 citation statements)

References 44 publications

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“…This inference has been proposed for IL-6 (71), IL-8 (72), FOX01 (73), and other mediators implicated in labor of humans. Although biologic effects of (heat-inactivated) Gram + bacteria are not fully reproduced by LTA (74), the latter do elicit many features of the bacteria (75); a similar argument can be made for (heat-inactivated) Gram 2 bacteria and LPS (76), including as it applies to placental/fetal biology (66).…”

Section: Discussionmentioning

confidence: 92%

Novel Noncompetitive IL-1 Receptor–Biased Ligand Prevents Infection- and Inflammation-Induced Preterm Birth

Nadeau-Vallée

Quiniou

Palacios

et al. 2015

The Journal of Immunology

101

123

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Preterm birth (PTB) is firmly linked to inflammation regardless of the presence of infection. Proinflammatory cytokines, including IL-1β, are produced in gestational tissues and can locally upregulate uterine activation proteins. Premature activation of the uterus by inflammation may lead to PTB, and IL-1 has been identified as a key inducer of this condition. However, all currently available IL-1 inhibitors are large molecules that exhibit competitive antagonism properties by inhibiting all IL-1R signaling, including transcription factor NF-κB, which conveys important physiological roles. We hereby demonstrate the efficacy of a small noncompetitive (all-d peptide) IL-1R–biased ligand, termed rytvela (labeled 101.10) in delaying IL-1β–, TLR2-, and TLR4-induced PTB in mice. The 101.10 acts without significant inhibition of NF-κB, and instead selectively inhibits IL-1R downstream stress-associated protein kinases/transcription factor c-jun and Rho GTPase/Rho-associated coiled-coil–containing protein kinase signaling pathways. The 101.10 is effective at decreasing proinflammatory and/or prolabor genes in myometrium tissue and circulating leukocytes in all PTB models independently of NF-κB, undermining NF-κB role in preterm labor. In this work, biased signaling modulation of IL-1R by 101.10 uncovers a novel strategy to prevent PTB without inhibiting NF-κB.

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Section: Discussionmentioning

confidence: 92%

Novel Noncompetitive IL-1 Receptor–Biased Ligand Prevents Infection- and Inflammation-Induced Preterm Birth

Nadeau-Vallée

Quiniou

Palacios

et al. 2015

The Journal of Immunology

101

123

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“…These reports suggest that MSCmicrobe interactions occur, but specific and direct evidence of these interactions and their influence on the immunomodulatory capacity of MSCs remains elusive. Recently, Fiedler et al determined that MSCs can interact with common skinassociated bacteria, but their exact interaction and their effect on immunomodulatory properties were not determined [25]. In individuals with intestinal inflammation who receive MSC therapy, microbes may contribute to the engrafted MSC's niche and, along with other mediators, participate in determining whether administered MSCs will adopt an antiinflammatory or a proinflammatory phenotype [19,[26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Gastrointestinal Microbes Interact with Canine Adipose-Derived Mesenchymal Stem Cells In Vitro and Enhance Immunomodulatory Functions

Kol

Foutouhi

Walker

et al. 2014

Stem Cells and Development

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Mesenchymal stem cells (MSCs) are somatic, multipotent stromal cells with potent immunomodulatory and regenerative properties. Although MSCs have pattern recognition receptors and are modulated by Toll-like receptor ligands, MSC-microbial interactions are poorly defined. The objectives of this study were to determine the effect of bacterial association on MSC function. We hypothesized that gastrointestinal bacteria associate with MSCs and alter their immunomodulatory properties. The effect of MSC-microbial interactions on MSC morphology, viability, proliferation, migration, and immunomodulatory functions was investigated. MSCs associated with a remarkable array of enteric pathogens and commensal bacteria. MSC interactions with two model organisms, the pathogen Salmonella typhimurium and the probiotic Lactobacillus acidophilus, were further investigated. While ST readily invaded MSCs, LB adhered to the MSC plasma membrane. Neither microbe induced MSC death, degeneration, or diminished proliferation. Microbial association did not upregulate MHC-II, CD80/86, or CD1 expression. MSCmicrobial interaction significantly increased transcription of key immunomodulatory genes, including COX2, IL6, and IL8, coupled with significantly increased prostaglandin E 2 (PGE 2 ), interleukin (IL)6, and IL8 secretion. MSC-ST coincubation resulted in increased MSC expression of CD54, and significant augmentation of MSC inhibition of mitogen-induced T-cell proliferation. T-cell proliferation was partially restored when PGE 2 secretion was blocked from ST-primed MSCs. MSC-microbe interactions have a profound effect on MSC function and may be pivotal in a variety of clinical settings where MSCs are being explored as potential therapeutics in the context of microbial communities, such as Crohn's disease, chronic nonhealing wounds, and sepsis.

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“…Another study showed that mesenchymal stem cells (MSCs) are recruited at the site of infection and suppress T-cell responses by producing nitric oxide (8). MSCs are susceptible to infection by several other intracellular pathogens as well (9). Recent studies have shown that MSCs possess antimicrobial properties against Gram-positive and Gram-negative bacterial infections and also improve the survival of mice with bacterial infections (10).…”

mentioning

confidence: 99%

Mouse Bone Marrow Sca-1 ⁺ CD44 ⁺ Mesenchymal Stem Cells Kill Avirulent Mycobacteria but Not Mycobacterium tuberculosis through Modulation of Cathelicidin Expression via the p38 Mitogen-Activated Protein Kinase-Dependent Pathway

et al. 2017

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Mycobacterium tuberculosis primarily infects lung macrophages. However, a recent study showed that M. tuberculosis also infects and persists in a dormant form inside bone marrow mesenchymal stem cells (BM-MSCs) even after successful antibiotic therapy. However, the mechanism(s) by which M. tuberculosis survives in BM-MSCs is still not known. Like macrophages, BM-MSCs do not contain a well-defined endocytic pathway, which is known to play a central role in the clearance of internalized mycobacteria. Here, we studied the fate of virulent and avirulent mycobacteria in Sca-1 ϩ CD44 ϩ BM-MSCs. We found that BM-MSCs were able to kill avirulent Mycobacterium smegmatis and Mycobacterium bovis BCG but not the pathogenic species M. tuberculosis. Further mechanistic studies revealed that pathogenic M. tuberculosis dampens the antibacterial response of BM-MSCs by downregulating the expression of the cationic antimicrobial peptide cathelicidin. In contrast, avirulent mycobacteria were effectively killed by inducing the Toll-like receptor 2/4 (TLR2/4) pathway-dependent expression of cathelicidin, while small interfering RNA (siRNA)-mediated cathelicidin silencing increased the survival of M. bovis BCG in BMMSCs. We also showed that M. bovis BCG infection caused increased expression levels of MyD88, phospho-interleukin-1 receptor-associated kinase 4 (pIRAK-4), and the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Further downstream investigations demonstrated that IRAK-4 -p38 activation increased the nuclear translocation of NF-B, which subsequently induced the expression of cathelicidin and the cytokine interleukin-1␤ (IL-1␤), resulting in the decreased survival of M. bovis BCG. On the other hand, inhibition of TLR2/4, pIRAK-4, p38, and NF-B nuclear translocation decreased cathelicidin and IL-1␤ expression levels and therefore increased the survival of avirulent mycobacteria. This is the first report that demonstrates that virulent mycobacteria manipulate the TLR2/4 -MyD88 -IRAK-4 -p38 -NF-B-Camp-IL-1␤ pathway to survive inside bone marrow stem cells.

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Impact of bacteria and bacterial components on osteogenic and adipogenic differentiation of adipose-derived mesenchymal stem cells

Cited by 63 publications

References 44 publications

Novel Noncompetitive IL-1 Receptor–Biased Ligand Prevents Infection- and Inflammation-Induced Preterm Birth

Novel Noncompetitive IL-1 Receptor–Biased Ligand Prevents Infection- and Inflammation-Induced Preterm Birth

Gastrointestinal Microbes Interact with Canine Adipose-Derived Mesenchymal Stem Cells In Vitro and Enhance Immunomodulatory Functions

Mouse Bone Marrow Sca-1 ⁺ CD44 ⁺ Mesenchymal Stem Cells Kill Avirulent Mycobacteria but Not Mycobacterium tuberculosis through Modulation of Cathelicidin Expression via the p38 Mitogen-Activated Protein Kinase-Dependent Pathway

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Impact of bacteria and bacterial components on osteogenic and adipogenic differentiation of adipose-derived mesenchymal stem cells

Cited by 63 publications

References 44 publications

Novel Noncompetitive IL-1 Receptor–Biased Ligand Prevents Infection- and Inflammation-Induced Preterm Birth

Novel Noncompetitive IL-1 Receptor–Biased Ligand Prevents Infection- and Inflammation-Induced Preterm Birth

Gastrointestinal Microbes Interact with Canine Adipose-Derived Mesenchymal Stem Cells In Vitro and Enhance Immunomodulatory Functions

Mouse Bone Marrow Sca-1 + CD44 + Mesenchymal Stem Cells Kill Avirulent Mycobacteria but Not Mycobacterium tuberculosis through Modulation of Cathelicidin Expression via the p38 Mitogen-Activated Protein Kinase-Dependent Pathway

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Mouse Bone Marrow Sca-1 ⁺ CD44 ⁺ Mesenchymal Stem Cells Kill Avirulent Mycobacteria but Not Mycobacterium tuberculosis through Modulation of Cathelicidin Expression via the p38 Mitogen-Activated Protein Kinase-Dependent Pathway