Marrow mesenchymal stromal cells reduce methicillin-resistant Staphylococcus aureus infection in rat models

Yuan, Yuan; Lin, Songyi; Guo, Na; Zhao, Cheng; Shen, Suxia; Bu, Xiujuan; Ye, Haiqing

doi:10.1016/j.jcyt.2013.06.002

Cited by 45 publications

(48 citation statements)

References 33 publications

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“…In addition, previous studies have demonstrated that MSCs may participate in the mitigation of infection by secretion of soluble paracrine factors including interleukin (IL)-10 [24], prostaglandin E 2 (PGE 2 ) [25], tumor necrosis factor (TNF)-α-stimulated gene/protein 6 [26], and IL-6 [27]. A previous study investigating the antibacterial effects of MSCs on a subcutaneous infected rat model indicated a higher reduction of MRSA count compared to our present findings [12]. This observation could be explained by the amount of cells administered into the host animals.…”

Section: Discussionsupporting

confidence: 43%

“…Furthermore, MSCs have also been demonstrated to secrete the antimicrobial peptide (AMP) LL-37 when challenged with Escherichia coli in an in vivo mouse pneumonia model [11]. In terms of skin infections, MSCs introduced by intravenous tail injection into subcutaneous MRSA-infected rats were able to reduce the bacterial load in a dose-dependent manner [12]. …”

Section: Introductionmentioning

confidence: 99%

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Synergistic antibacterial effect of co-administering adipose-derived mesenchymal stromal cells and Ophiophagus hannah l-amino acid oxidase in a mouse model of methicillin-resistant Staphylococcus aureus-infected wounds

2017

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BackgroundMesenchymal stromal cells (MSCs) and Ophiophagus hannah l-amino acid oxidase (Oh-LAAO) have been reported to exhibit antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA). Published data have indicated that synergistic antibacterial effects could be achieved by co-administration of two or more antimicrobial agents. However, this hypothesis has not been proven in a cell- and protein-based combination. In this study, we investigate if co-administration of adipose-derived MSCs and Oh-LAAO into a mouse model of MRSA-infected wounds would be able to result in a synergistic antibacterial effect.MethodsMSCs and Oh-LAAO were isolated and characterized by standard methodologies. The effects of the experimental therapies were evaluated in C57/BL6 mice. The animal study groups consisted of full-thickness uninfected and MRSA-infected wound models which received Oh-LAAO, MSCs, or both. Oh-LAAO was administered directly on the wound while MSCs were delivered via intradermal injections. The animals were housed individually with wound measurements taken on days 0, 3, and 7. Histological analyses and bacterial enumeration were performed on wound biopsies to determine the efficacy of each treatment.ResultsImmunophenotyping and differentiation assays conducted on isolated MSCs indicated expression of standard cell surface markers and plasticity which corresponds to published data. Characterization of Oh-LAAO by proteomics, enzymatic, and antibacterial assays confirmed the identity, purity, and functionality of the enzyme prior to use in our subsequent studies. Individual treatments with MSCs and Oh-LAAO in the infected model resulted in reduction of MRSA load by one order of magnitude to the approximate range of 6 log10 colony-forming units (CFU) compared to untreated controls (7.3 log10 CFU). Similar wound healing and improvements in histological parameters were observed between the two groups. Co-administration of MSCs and Oh-LAAO reduced bacterial burden by approximately two orders of magnitude to 5.1 log10 CFU. Wound closure measurements and histology analysis of biopsies obtained from the combinational therapy group indicated significant enhancement in the wound healing process compared to all other groups.ConclusionsWe demonstrated that co-administration of MSCs and Oh-LAAO into a mouse model of MRSA-infected wounds exhibited a synergistic antibacterial effect which significantly reduced the bacterial count and accelerated the wound healing process.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0457-2) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 43%

Section: Introductionmentioning

confidence: 99%

Synergistic antibacterial effect of co-administering adipose-derived mesenchymal stromal cells and Ophiophagus hannah l-amino acid oxidase in a mouse model of methicillin-resistant Staphylococcus aureus-infected wounds

2017

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“…Gram-negative pathogens are not the only pathogens that can be treated with MSC therapy. In rats infected with methicillin-resistant Staphylococcus aureus, BMSCs reduced the number of bacteria and blunted the production of inflammatory cytokines and chemokines augmenting wound healing [22].…”

Section: In Vivo Antibacterial Effectsmentioning

confidence: 97%

“…and may also start producing novel cytokines such as TNF-␣, IL-1␤ or IL-10 [15,[18][19][20][21][22].…”

Section: Pathogens Alter Msc Biologymentioning

confidence: 99%

Mesenchymal stem cells and infectious diseases: Smarter than drugs

Mezey

Nemeth

2015

Immunology Letters

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“…MSC transplant has been protective in preclinical animal models of polymicrobial sepsis[282,270] as well as in infections caused by bacterial strains of Escherichia coli , Pseudomonas aeruginosa and Staphylococcus aureus [266,284,362]. The protective role of MSCs in sepsis has been mainly attributed to their broad paracrine modulatory properties[269].…”

Section: Immunomodulatory Oligonucleotide Imt504 and Inflammatory Dismentioning

confidence: 99%

Immunomodulatory oligonucleotide IMT504: Effects on mesenchymal stem cells as a first-in-class immunoprotective/immunoregenerative therapy

Zorzopulos¹,

Opal²,

Hernando-Insúa³

et al. 2017

WJSC

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The immune responses of humans and animals to insults (i.e., infections, traumas, tumoral transformation and radiation) are based on an intricate network of cells and chemical messengers. Abnormally high inflammation immediately after insult or abnormally prolonged pro-inflammatory stimuli bringing about chronic inflammation can lead to life-threatening or severely debilitating diseases. Mesenchymal stem cell (MSC) transplant has proved to be an effective therapy in preclinical studies which evaluated a vast diversity of inflammatory conditions. MSCs lead to resolution of inflammation, preparation for regeneration and actual regeneration, and then ultimate return to normal baseline or homeostasis. However, in clinical trials of transplanted MSCs, the expectations of great medical benefit have not yet been fulfilled. As a practical alternative to MSC transplant, a synthetic drug with the capacity to boost endogenous MSC expansion and/or activation may also be effective. Regarding this, IMT504, the prototype of a major class of immunomodulatory oligonucleotides, induces in vivo expansion of MSCs, resulting in a marked improvement in preclinical models of neuropathic pain, osteoporosis, diabetes and sepsis. IMT504 is easily manufactured and has an excellent preclinical safety record. In the small number of patients studied thus far, IMT504 has been well-tolerated, even at very high dosage. Further clinical investigation is necessary to demonstrate the utility of IMT504 for resolution of inflammation and regeneration in a broad array of human diseases that would likely benefit from an immunoprotective/immunoregenerative therapy.

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Marrow mesenchymal stromal cells reduce methicillin-resistant Staphylococcus aureus infection in rat models

Cited by 45 publications

References 33 publications

Synergistic antibacterial effect of co-administering adipose-derived mesenchymal stromal cells and Ophiophagus hannah l-amino acid oxidase in a mouse model of methicillin-resistant Staphylococcus aureus-infected wounds

Synergistic antibacterial effect of co-administering adipose-derived mesenchymal stromal cells and Ophiophagus hannah l-amino acid oxidase in a mouse model of methicillin-resistant Staphylococcus aureus-infected wounds

Mesenchymal stem cells and infectious diseases: Smarter than drugs

Immunomodulatory oligonucleotide IMT504: Effects on mesenchymal stem cells as a first-in-class immunoprotective/immunoregenerative therapy

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