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

Walter, James M.; Ware, Lorraine B.; Matthay, Michael A.

doi:10.1016/s2213-2600(14)70217-6

Cited by 230 publications

(215 citation statements)

References 91 publications

Supporting

Mentioning

212

Contrasting

Unclassified

Order By: Relevance

“…Allogeneic MSC therapy has beneficial preclinical effects on endotoxin-, bacteria-, and ventilator-induced acute lung injury (9) via MSC secretion of the soluble paracrine growth factors angiopoietin-1 (Ang1) and keratinocyte growth factor (KGF) (9,10). MSCs can also transfer mitochondria and microvesicles that modulate immunity and epithelial response to injury (11).…”

mentioning

confidence: 99%

Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

Chan

Kuok

Leung

et al. 2016

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

178

176

View full text Add to dashboard Cite

Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium’s protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.

show abstract

mentioning

confidence: 99%

Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

Chan

Kuok

Leung

et al. 2016

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

178

176

View full text Add to dashboard Cite

show abstract

“…Investigators have begun to explore cell-based therapies for numerous disease processes, including sepsis and lung injury (1). Mesenchymal stromal cells (MSCs) are known to have immunomodulatory properties and are thought to be immune privileged, making them an attractive candidate for this type of therapy.…”

mentioning

confidence: 99%

Mesenchymal Stromal Cells Deficient in Autophagy Proteins Are Susceptible to Oxidative Injury and Mitochondrial Dysfunction

Ghanta

Tsoyi

Liu

et al. 2017

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Oxidative stress resulting from inflammatory responses that occur during acute lung injury and sepsis can initiate changes in mitochondrial function. Autophagy regulates cellular processes in the setting of acute lung injury, sepsis, and oxidative stress by modulating the immune response and facilitating turnover of damaged cellular components. We have shown that mesenchymal stromal cells (MSCs) improve survival in murine models of sepsis by also regulating the immune response. However, the effect of autophagy on MSCs and MSC mitochondrial function during oxidative stress is unknown. This study investigated the effect of depletion of autophagic protein microtubule-associated protein 1 light chain 3B (LC3B) and beclin 1 (BECN1) on the response of MSCs to oxidative stress. MSCs were isolated from wild-type (WT) and LC3B 2/2 or Becn1 1/2 mice. MSCs from the LC3B 2/2 and Becn1 1/2 animals had increased susceptibility to oxidative stress-induced cell death as compared with WT MSCs. The MSCs depleted of autophagic proteins also had impaired mitochondrial function (decreased intracellular ATP, reduced mitochondrial membrane potential, and increased mitochondrial reactive oxygen species production) under oxidative stress as compared with WT MSCs. In WT MSCs, carbon monoxide (CO) preconditioning enhanced autophagy and mitophagy, and rescued the cells from oxidative stress-induced death. CO preconditioning was not able to rescue the decreased survival of MSCs from the LC3B 2/2 and Becn1 1/2 animals, further supporting the tenet that CO exerts its cytoprotective effects via the autophagy pathway.

show abstract

“…GM-CSF use was also associated with nonsignificant decreases in the duration of mechanical ventilation, ICU and hospital length of stay, and improvements in APACHE II scores when compared to placebo [67]. In addition, mesenchymal stem cells have been associated with anti-inflammatory, immunomodulatory, antiapoptotic, and antimicrobial properties [68]. A phase I clinical trial in patients with infections who were admitted to the ICU is ongoing (NCT 02421484).…”

Section: Management Of Organism and Organism Toxicity In Septic Shockmentioning

confidence: 99%

The Understanding and Management of Organism Toxicity in Septic Shock

Genga¹,

Shimada²,

Boyd

et al. 2018

J Innate Immun

View full text Add to dashboard Cite

The toxicity caused by different organisms in septic shock is substantially complex and characterized by an intricate pathogenicity that involves several systems and pathways. Immune cells’ pattern recognition receptors initiate the host response to pathogens after the recognition of pathogen-associated molecular patterns. In essence, the subsequent activation of downstream pathways may progress to infection resolution or to a dysregulated host response that represents the hallmark of organ injury in septic shock. Likewise, the management of organism toxicity in septic shock is complicated and comprises a multiplicity of suitable targets. In this review, the classic immune responses to pathogens are discussed as well as other factors that are relevant in the pathogenicity of septic shock, including sepsis-induced immune suppression, inflammasome activation, intestinal permeability, and the role of lipids and proprotein convertase subtilisin/kexin type 9. Current therapies aiming to eliminate the organisms causing septic shock, recent and ongoing trials in septic shock treatment, and potential new therapeutic strategies are also explored.

show abstract

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

Cited by 230 publications

References 91 publications

Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

Mesenchymal Stromal Cells Deficient in Autophagy Proteins Are Susceptible to Oxidative Injury and Mitochondrial Dysfunction

The Understanding and Management of Organism Toxicity in Septic Shock

Contact Info

Product

Resources

About