Emerging roles for multipotent, bone marrow–derived stromal cells in host defense

Auletta, Jeffery J.; Deans, Robert; Bartholomew, Amelia

doi:10.1182/blood-2011-10-384354

Cited by 91 publications

(100 citation statements)

References 90 publications

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“…Although the mechanism by which IL-17 + MSCs upregulate Th17 cells is unknown, the interplay between donor MSCs and recipient microenvironment may determine MSC-based immunomodulatory response [33,41]. Our findings imply that MSC-based immunomodulation is regulated by different subsets of MSCs, in which they may exert either immunosuppressive or immunostimulatory functions.…”

Section: Discussionmentioning

confidence: 69%

A subset of IL-17+ mesenchymal stem cells possesses anti-Candida albicans effect

et al. 2012

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Section: Discussionmentioning

confidence: 69%

A subset of IL-17+ mesenchymal stem cells possesses anti-Candida albicans effect

et al. 2012

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“…Recent studies showed that MSCs are located in the perivascular niche and constitute a subset of pericytes that are involved in both pathogen recognition and early inflammatory events (3). MSCs seem to impede pathogen growth and reduce the microbial burden by inhibiting growth through soluble factors or by enhancing the antimicrobial function of immune cells, as shown both in vitro and in vivo (2)(3)(4)(5). For example, Nemeth et al reported that mouse MSCs (mMSCs) prolonged the survival of septic mice and improved their organ (kidney, liver, and pancreas) functions (5).…”

mentioning

confidence: 99%

“…MSCs have been successfully used to prevent and treat immune disorders, such as graft-versus-host disease, and emerging preclinical studies suggest that they might also protect against infectious challenges (1,2). Recent studies showed that MSCs are located in the perivascular niche and constitute a subset of pericytes that are involved in both pathogen recognition and early inflammatory events (3).…”

mentioning

confidence: 99%

Guanylate-binding protein 1 (GBP1) contributes to the immunity of human mesenchymal stromal cells against Toxoplasma gondii

Qin

Lai

Liu

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Mesenchymal stromal cells (MSCs) have recently been shown to play important roles in mammalian host defenses against intracellular pathogens, but the molecular mechanism still needs to be clarified. We confirmed that human MSCs (hMSCs) prestimulated with IFN-γ showed a significant and dose-dependent ability to inhibit the growth of two types of Toxoplasma gondii [type I RH strain with green fluorescent proteins (RH/GFP) or type II PLK strain with red fluorescent proteins (PLK/RED)]. However, in contrast to previous reports, the anti-T. gondii activity of hMSCs was not mediated by indoleamine 2,3-dioxygenase (IDO). Genome-wide RNA sequencing (RNA-seq) analysis revealed that IFN-γ increased the expression of the p65 family of human guanylate-binding proteins (hGBPs) in hMSCs, especially hGBP1. To analyze the functional role of hGBPs, stable knockdowns of hGBP1, -2, and -5 in hMSCs were established using a lentiviral transfection system. hGBP1 knockdown in hMSCs resulted in a significant loss of the anti-T. gondii host defense property, compared with hMSCs infected with nontargeted control sequences. hGBP2 and -5 knockdowns had no effect. Moreover, the hGBP1 accumulation on the parasitophorous vacuole (PV) membranes of IFN-γ-stimulated hMSCs might protect against T. gondii infection. Taken together, our results suggest that hGBP1 plays a pivotal role in anti-T. gondii protection of hMSCs and may shed new light on clarifying the mechanism of host defense properties of hMSCs.human stem cells | parasitic protozoan | innate immunity | in vitro cultivation

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“…Human BMSCs could also promote the alternative activation of infiltrated rat macrophage when they were locally transplanted at the injured spinal cord site (Nakajima et al, 2012). Additionally, MSC-mediated polarization of M2 macrophages displays increased phagocytic and antimicrobial activities (Kim and Hematti, 2009;Nemeth et al, 2009;Maggini et al, 2010;Zhang et al, 2010), which may contribute to the emerging role of MSCs in host defense against infectious challenges (Auletta et al, 2012), as evidenced in a mouse model for sepsis (Nemeth et al, 2009;Krasnodembskaya et al, 2012) and zymozan-induced peritonitis (Bartosh et al, 2010;Choi et al, 2011). Likewise, GMSCs were shown to be capable of polarizing macrophages into the M2 phenotype via enhanced secretion of IL-6 and GM-CSF (Zhang et al, 2010) (Fig.…”

Section: Macrophagesmentioning

confidence: 99%

Human Oral Mucosa and Gingiva

et al. 2012

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Mesenchymal stem cells (MSCs) represent a heterogeneous population of progenitor cells with self-renewal and multipotent differentiation potential. Aside from their regenerative role, extensive in vitro and in vivo studies have demonstrated that MSCs are capable of potent immunomodulatory effects on a variety of innate and adaptive immune cells. In this article, we will review recent experimental studies on the characterization of a unique population of MSCs derived from human oral mucosa and gingiva, especially their immunomodulatory and anti-inflammatory functions and their application in the treatment of several in vivo models of inflammatory diseases. The ease of isolation, accessible tissue source, and rapid ex vivo expansion, with maintenance of stable stem-celllike phenotypes, render oral mucosa-and gingivaderived MSCs a promising alternative cell source for MSC-based therapies.

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Emerging roles for multipotent, bone marrow–derived stromal cells in host defense

Cited by 91 publications

References 90 publications

A subset of IL-17+ mesenchymal stem cells possesses anti-Candida albicans effect

A subset of IL-17+ mesenchymal stem cells possesses anti-Candida albicans effect

Guanylate-binding protein 1 (GBP1) contributes to the immunity of human mesenchymal stromal cells against Toxoplasma gondii

Human Oral Mucosa and Gingiva

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