Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes

Krasnodembskaya, Anna; Samarani, Gianluca; Song, Yuanlin; Zhuo, Hanjing; Su, Xiao; Lee, Jae Woo; Gupta, Naveen; Petrini, Mario; Matthay, Michael A.

doi:10.1152/ajplung.00180.2011

Cited by 280 publications

(285 citation statements)

References 41 publications

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“…MSCs were able to increase the proportion of phagocytic MDMs in the presence of LPS ( Figure 1D). This adds to the body of literature supporting the phagocytosis-enhancing effects of MSCs on both macrophages and monocytes (8,10,19,27).…”

Section: Msc-derived Ev-treated Murine Amsmentioning

confidence: 63%

“…Mesenchymal stromal cells (MSCs) are increasingly recognized as a promising candidate therapy for ARDS (6). We and others have reported that MSCs improve survival, reduce inflammation, and enhance bacterial clearance in preclinical models of lung injury (7)(8)(9)(10)(11)(12)(13)(14). Secretion of paracrine factors, modulation of host cells via secretion of extracellular vesicles (EVs), and mitochondrial transfer were shown to be important for the therapeutic effects of MSCs in these studies.…”

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confidence: 90%

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Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer

Morrison

Jackson

Cunningham

et al. 2017

Am J Respir Crit Care Med

541

470

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Rationale: Acute respiratory distress syndrome (ARDS) remains a major cause of respiratory failure in critically ill patients. Mesenchymal stromal cells (MSCs) are a promising candidate for a cell-based therapy. However, the mechanisms of MSCs' effects in ARDS are not well understood. In this study, we focused on the paracrine effect of MSCs on macrophage polarization and the role of extracellular vesicle (EV)-mediated mitochondrial transfer.Objectives: To determine the effects of human MSCs on macrophage function in the ARDS environment and to elucidate the mechanisms of these effects.Methods: Human monocyte-derived macrophages (MDMs) were studied in noncontact coculture with human MSCs when stimulated with LPS or bronchoalveolar lavage fluid (BALF) from patients with ARDS. Murine alveolar macrophages (AMs) were cultured ex vivo with/without human MSC-derived EVs before adoptive transfer to LPS-injured mice.Measurements and Main Results: MSCs suppressed cytokine production, increased M2 macrophage marker expression, and augmented phagocytic capacity of human MDMs stimulated with LPS or ARDS BALF. These effects were partially mediated by CD44-expressing EVs. Adoptive transfer of AMs pretreated with MSCderived EVs reduced inflammation and lung injury in LPS-injured mice. Inhibition of oxidative phosphorylation in MDMs prevented the modulatory effects of MSCs. Generating dysfunctional mitochondria in MSCs using rhodamine 6G pretreatment also abrogated these effects.Conclusions: In the ARDS environment, MSCs promote an antiinflammatory and highly phagocytic macrophage phenotype through EV-mediated mitochondrial transfer. MSC-induced changes in macrophage phenotype critically depend on enhancement of macrophage oxidative phosphorylation. AMs treated with MSCderived EVs ameliorate lung injury in vivo.

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Section: Msc-derived Ev-treated Murine Amsmentioning

confidence: 63%

mentioning

confidence: 90%

Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer

Morrison

Jackson

Cunningham

et al. 2017

Am J Respir Crit Care Med

541

470

View full text Add to dashboard Cite

show abstract

“…37,38,[48][49][50][51] This antibacterial eff ect is partly mediated by improved phagocytic activity of host immune cells such as macrophages, 38,41 monocytes, 48 neutrophils, 49 and ITGAMpositive cells (monocytes, macrophages, and neutrophils). 38 Studies using ex-vivo human lungs have reported similar fi ndings.…”

Section: Antimicrobial Eff Ectsmentioning

confidence: 99%

Mesenchymal stem cells: mechanisms of potential therapeutic benefit in ARDS and sepsis

Walter

Ware

Matthay

2014

The Lancet Respiratory Medicine

230

207

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“…Como placebo se utilizó una inyección de fibroblastos, suero salino o MSC inactivados por shock térmico. El tratamiento de soporte consistió en antibióticos y volumen, los que fueron administrados a los grupos experimental y placebo [24][25][26][27][28][29] . El momento de la infusión y la dosis de MSCs fue variable entre los estudios.…”

Section: Sepsisunclassified

Escenario actual y perspectivas de la terapia con células madre mesenquimales en medicina intensiva

2016

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Overview and perspectives of mesenchymal stem cell therapy in intensive care medicine El grupo más ominoso está integrado por aquellos pacientes que cursan con sepsis severa o shock séptico, síndrome de distrés respiratorio agudo (SDRA) e/o injuria renal aguda (IRA).La mortalidad es considerablemente elevada, alcanzando 45% en el SDRA grave y 18,4% en la sepsis severa 1,2 . En el campo farmacológico no han existido avances sustanciales y los esfuerzos globales se han enfocado en la implementación de protocolos de diagnóstico precoz y de tratamientos basados en metas. Estas medidas han contribuido a una disminución de la mortalidad, pero no han cambiado sustancialmente el pronóstico.En este contexto, un cambio en el enfrentamiento terapéutico parece fundamental. La terapia celular, específicamente el uso de células madre mesenquimales (MSC), surge como una opción dado su potencial inmunomodulador y regenerativo. Los datos preclínicos son positivos y han dado pie a la realización de los primeros ensayos clínicos en sepsis, SDRA e IRA.El objetivo del artículo es ofrecer una visión al clínico de la realidad actual de la terapia celular en medicina intensiva. Para ello se ha realizado una descripción de las propiedades, funciones y fuentes de las MSC para, posteriormente, abordar la evidencia en modelos preclínicos y los estudios clínicos en tres patologías: sepsis, SDRA e IRA.

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Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes

Abstract: MA. Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes. Am

Cited by 280 publications

References 41 publications

Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer

Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer

Mesenchymal stem cells: mechanisms of potential therapeutic benefit in ARDS and sepsis

Escenario actual y perspectivas de la terapia con células madre mesenquimales en medicina intensiva

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