Could stem cells be the future therapy for sepsis?

Kingsley, S. Manoj Kumar; Bhat, B. Vishnu

doi:10.1016/j.blre.2016.05.004

Cited by 12 publications

(16 citation statements)

References 224 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sepsis is associated with elevated plasma levels of nucleosomes, which is considered to reflect enhanced cell death . Considering that ASCs exert antiapoptotic effects , we were interested to determine the impact of ASC infusion on nucleosome release during endotoxemia. Intravenous LPS elicited a transient rise in plasma nucleosome levels peaking after 3 hours (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In recent years, MSCs have emerged as potent therapeutic tools based on their capacity to modulate immune responses and their low immunogenicity . MSCs can exert many different immunomodulatory effects that theoretically could be beneficial in sepsis, including inhibition of microbial growth, reduction of pro‐inflammatory cytokine release with concurrent enhancement of anti‐inflammatory cytokine production, attenuation of inflammatory cell adhesion to endothelium, stimulation of endothelial regeneration, and inhibition of apoptosis . In accordance, treatment with MSCs improved a variety of outcome parameters in animal models of sepsis .…”

Section: Introductionmentioning

confidence: 99%

“…As such, there is a need for newer therapeutic approaches. Adult mesenchymal stem cells (MSCs) could potentially have clinical relevance in this context .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Intravenous Infusion of Human Adipose Mesenchymal Stem Cells Modifies the Host Response to Lipopolysaccharide in Humans: A Randomized, Single-Blind, Parallel Group, Placebo Controlled Trial

et al. 2018

View full text Add to dashboard Cite

In experimental models, mesenchymal stem cells (MSCs) can modulate various immune responses implicated in the pathogenesis of sepsis. Intravenous injection of lipopolysaccharide (LPS) into healthy subjects represents a model with relevance for the host response to sepsis. To explore the use of MSCs in sepsis, we determined their effect on the response to intravenous LPS in a randomized study in 32 healthy subjects with four treatment arms: placebo or allogeneic adipose MSCs (ASCs) intravenously at either 0.25 × 10 , 1 × 10 , or 4 × 10 cells/kg; all subjects received LPS intravenously (2 ng/kg) one hour after the end of ASC infusion (Trial Register number 2014-002537-63, clinicaltrials.gov identifier NCT02328612). Infusion of ASCs was well tolerated. The high ASC dose increased the febrile response, exerted mixed pro-inflammatory (enhanced interleukin-8 and nucleosome release) and anti-inflammatory effects (increased interleukin-10 and transforming growth factor-β release), and enhanced coagulation activation and reduced the fibrinolytic response. Blood leukocyte transcriptome analyses showed a biphasic effect of ASCs on the LPS response: at 2 hours post LPS, ASC-infused subjects displayed higher expression of genes involved in innate immune pathways, whereas at 4 hours post LPS these subjects had lower expression of innate immune pathway genes. Infusion of ASCs did not modify the "ex vivo" responsiveness of whole blood to various bacterial agonists. These results indicate that intravenous infusion of allogeneic ASCs (4 × 10 cells/kg) has a variety of proinflammatory, anti-inflammatory, and procoagulant effects during human endotoxemia. Further studies are needed to assess the safety and efficacy of ASCs in sepsis patients. Stem Cells 2018;36:1778-1788.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Intravenous Infusion of Human Adipose Mesenchymal Stem Cells Modifies the Host Response to Lipopolysaccharide in Humans: A Randomized, Single-Blind, Parallel Group, Placebo Controlled Trial

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Allogeneic mesenchymal stem or stromal cells (MSCs) have been shown to reduce organ dysfunction and mortality in animal models of sepsis by mechanisms that include antimicrobial, anti-apoptotic, immunomodulatory and barrier-preserving effects 134,135 . The anti microbial activity of MSCs is mediated by various antimicrobial proteins and peptides such as bacterial defensins, LL-37, lipocalin 2 (also known as NGAL) and keratinocyte growth factor (KGF; also known as FGF7).…”

Section: The Administration Of Mesenchymal Stem Cellsmentioning

confidence: 99%

“…The anti microbial activity of MSCs is mediated by various antimicrobial proteins and peptides such as bacterial defensins, LL-37, lipocalin 2 (also known as NGAL) and keratinocyte growth factor (KGF; also known as FGF7). Multiple mechanisms have been implicated in the anti-inflammatory effects of MSCs, including the induction of IL-10, KGF and TNFstimulated gene 6 protein (TSG6), and the inhibition of p38 mitogen-activated protein kinase [134][135][136][137] . The administration of MSCs to humans seems to be safe, and at least two early-phase trials in patients with sepsis are planned or have been initiated 138,139 .…”

Section: The Administration Of Mesenchymal Stem Cellsmentioning

confidence: 99%

The immunopathology of sepsis and potential therapeutic targets

et al. 2017

View full text Add to dashboard Cite

Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. In sepsis, the immune response that is initiated by an invading pathogen fails to return to homeostasis, thus culminating in a pathological syndrome that is characterized by sustained excessive inflammation and immune suppression. Our understanding of the key mechanisms involved in the pathogenesis of sepsis has increased tremendously, yet this still needs to be translated into novel targeted therapeutic strategies. Pivotal for the clinical development of new sepsis therapies is the selection of patients on the basis of biomarkers and/or functional defects that provide specific insights into the expression or activity of the therapeutic target.

show abstract

Allogeneic mesenchymal stromal cells: Novel therapeutic option for mutated FLNA‐associated respiratory failure in the pediatric setting

Pelizzo

Avanzini

Lenta

et al. 2019

Pediatric Pulmonology

View full text Add to dashboard Cite

BackgroundMesenchymal stromal cell (MSC)‐mediated therapeutic effects have been observed in the treatment of lung diseases. For the first time, this treatment was used as rescue therapy in a pediatric patient with a life‐threatening respiratory syndrome associated with the filamin A (FLNA) gene mutation.MethodsA child with a new pathogenic variant of the FLNA gene c.7391_7403del (p.Val2464AlafsTer5), at the age of 18 months, due to serious and irreversible chronic respiratory failure, was treated with repeated intravenous infusions of allogeneic bone marrow (BM)‐MSCs. The child's respiratory condition was monitored. Immunologic studies before each MSC treatment were performed.ResultsNo acute adverse events related to the MSC infusions were observed. After the second infusion, the child's respiratory condition progressively improved, with reduced necessity for mechanical ventilation support. A thorax computed tomography (CT) scan showed bilateral recovery of the basal parenchyma, anatomical‐functional alignment and aerial penetration improvement. After the first MSC administration, an increase in Th17 and FoxP3+ T percentages in the peripheral blood was observed. After the second MSC infusion, a significant rise in the Treg/Th17 ratio was noted, as well as an increased percentage of CD20+/CD19+ B lymphocytes and augmented PHA‐induced proliferation.DiscussionMSC infusions are a promising therapeutic modality for patients in respiratory failure, as observed in this pediatric patient with an FLNA mutation. MSCs may have an immunomodulatory effect and thus mitigate lung injury; although in this case, MSC antimicrobial effects may have synergistically impacted the clinical improvements. Further investigations are planned to establish the safety and efficacy of this treatment option for interstitial lung diseases in children.

show abstract

Could stem cells be the future therapy for sepsis?

Cited by 12 publications

References 224 publications

Intravenous Infusion of Human Adipose Mesenchymal Stem Cells Modifies the Host Response to Lipopolysaccharide in Humans: A Randomized, Single-Blind, Parallel Group, Placebo Controlled Trial

Intravenous Infusion of Human Adipose Mesenchymal Stem Cells Modifies the Host Response to Lipopolysaccharide in Humans: A Randomized, Single-Blind, Parallel Group, Placebo Controlled Trial

The immunopathology of sepsis and potential therapeutic targets

Allogeneic mesenchymal stromal cells: Novel therapeutic option for mutated FLNA‐associated respiratory failure in the pediatric setting

Contact Info

Product

Resources

About