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Cell therapy for the treatment of sepsis and acute respiratory distress syndrome.

ABSTRACT: Sepsis and acute respiratory distress syndrome (ARDS) are life threating diseases with high mortality and morbidity in all the critical care units around the world. After decades of research, and numerous pre-clinical and clinical trials, sepsis and ARDS remain without a specific and effective pharmacotherapy and essentially the management remains supportive. In the last years cell therapies gained potential as a therapeutic treatment for ARDS and sepsis. Based on numerous pre-clinical studies, there is a growing evidence of the potential benefits of cell based therapies for the treatment of sepsis and ARDS. Several cell types are used in the last years for the treatment of both syndromes showing high efficiency. Embryonic stem cells (ESC), multipotent stem (or stromal) cells (MSC) and epithelial progenitors cells (EpPC) have been used for both diseases. Nowadays, the major part of the pre-clinical studies are using MSC, however other relevant groups are also using induced pluripotent stem cells (iPSC) for the treatment of both syndromes and alveolar type II cells for ARDS treatment. Numerous questions need further study including: determining the best source for the progenitor cells isolation, their large scale production and cryopreservation. Also, the heterogeneity of patients with sepsis and ARDS is massive, and establish a target population or the stratification of the patients will help us to determine better the therapeutic effect of these cell therapies. In this review we are going to describe briefly the different cell types, their potential sources and characteristics and mechanism of action. Here, also we elucidate the results of several pre-clicinical and clinical studies in ARDS and in sepsis and the future directions of these studies.

SUBMITTER: Guillamat-Prats R

PROVIDER: S-EPMC5721220 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Cell therapy for the treatment of sepsis and acute respiratory distress syndrome.

Guillamat-Prats Raquel R Camprubí-Rimblas Marta M Bringué Josep J Tantinyà Neus N Artigas Antonio A

Annals of translational medicine 20171101 22

Sepsis and acute respiratory distress syndrome (ARDS) are life threating diseases with high mortality and morbidity in all the critical care units around the world. After decades of research, and numerous pre-clinical and clinical trials, sepsis and ARDS remain without a specific and effective pharmacotherapy and essentially the management remains supportive. In the last years cell therapies gained potential as a therapeutic treatment for ARDS and sepsis. Based on numerous pre-clinical studies, ...[more]

PMID: 29264363

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Project description:BackgroundIn the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS.MethodsWe conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure-free days to day 14.ResultsThe study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P=0.21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P=0.96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was associated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P=0.01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P=0.003). Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range.ConclusionsRosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction. (Funded by the National Heart, Lung, and Blood Institute and the Investigator-Sponsored Study Program of AstraZeneca; ClinicalTrials.gov number, NCT00979121.).

Project description:Background: Acute respiratory distress syndrome (ARDS) is an unresolved challenge in the field of respiratory and critical care, and the changes in the lung microbiome during the development of ARDS and their clinical diagnostic value remain unclear. This study aimed to explore the role of the lung microbiome in disease progression in patients with sepsis-induced ARDS and potential therapeutic targets. Methods: Patients with ARDS were divided into two groups according to the initial site of infection, intrapulmonary infection (ARDSp, 111 cases) and extrapulmonary infection (ARDSexp, 45 cases), and a total of 28 patients with mild pulmonary infections were enrolled as the control group. In this study, we sequenced the DNA in the bronchoalveolar lavage fluid collected from patients using metagenomic next-generation sequencing (mNGS) to analyze the changes in the lung microbiome in patients with different infectious site and prognosis and before and after antibiotic treatment. Results: The Shannon–Wiener index indicated a statistically significant reduction in microbial diversity in the ARDSp group compared with the ARDSexp and control groups. The ARDSp group was characterized by a reduction in microbiome diversity, mainly in the normal microbes of the lung, whereas the ARDSexp group was characterized by an increase in microbiome diversity, mainly in conditionally pathogenic bacteria and intestinal microbes. Further analysis showed that an increase in Bilophila is a potential risk factor for death in ARDSexp. An increase in Escherichia coli, Staphylococcus aureus, Candida albicans, enteric microbes, or conditional pathogens may be risk factors for death in ARDSp. In contrast, Hydrobacter may be a protective factor in ARDSp. Conclusion: Different initial sites of infection and prognoses are likely to affect the composition and diversity of the pulmonary microbiome in patients with septic ARDS. This study provides insights into disease development and exploration of potential therapeutic targets.

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Cell therapy for the treatment of sepsis and acute respiratory distress syndrome.

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Cell therapy for the treatment of sepsis and acute respiratory distress syndrome.

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