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Clinical review: Stem cell therapies for acute lung injury/acute respiratory distress syndrome - hope or hype?

ABSTRACT: A growing understanding of the complexity of the pathophysiology of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), coupled with advances in stem cell biology, has led to a renewed interest in the therapeutic potential of stem cells for this devastating disease. Mesenchymal stem cells appear closest to clinical translation, given the evidence that they may favourably modulate the immune response to reduce lung injury, while maintaining host immune-competence and also facilitating lung regeneration and repair. The demonstration that human mesenchymal stem cells exert benefit in the endotoxin-injured human lung is particularly persuasive. Endothelial progenitor cells also demonstrate promise in reducing endothelial damage, which is a key pathophysiological feature of ALI. Embryonic and induced pluripotent stem cells are at an earlier stage in the translational process, but offer the hope of directly replacing injured lung tissue. The lung itself also contains endogenous stem cells, which may ultimately offer the greatest hope for lung diseases, given their physiologic role in replacing and regenerating native lung tissues. However, significant deficits remain in our knowledge regarding the mechanisms of action of stem cells, their efficacy in relevant pre-clinical models, and their safety, particularly in critically ill patients. These gaps need to be addressed before the enormous therapeutic potential of stem cells for ALI/ARDS can be realised.

SUBMITTER: Hayes M

PROVIDER: S-EPMC3681334 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Clinical review: Stem cell therapies for acute lung injury/acute respiratory distress syndrome - hope or hype?

Hayes Mairead M Curley Gerard G Ansari Bilal B Laffey John G JG

Critical care (London, England) 20121212 2

A growing understanding of the complexity of the pathophysiology of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), coupled with advances in stem cell biology, has led to a renewed interest in the therapeutic potential of stem cells for this devastating disease. Mesenchymal stem cells appear closest to clinical translation, given the evidence that they may favourably modulate the immune response to reduce lung injury, while maintaining host immune-competence and also facilita ...[more]

PMID: 22424108

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Project description:BACKGROUND:Acute kidney injury (AKI) is the most frequent extra-pulmonary organ failure in acute respiratory distress syndrome (ARDS). The objective of this study was to assess the factors associated with the development and severity of AKI in patients with ARDS. METHODS:This is a retrospective cohort study of ARDS patients without acute or chronic kidney disease prior to the onset of ARDS over a 7-year period (2010-2017). AKI and severity of AKI were defined according to the Kidney Disease Improving Global Outcomes 2012 guidelines. RESULTS:Of the 634 ARDS patients, 357 patients met study criteria. A total of 244 (68.3%) patients developed AKI after ARDS onset: 60 (24.6%) had stage I AKI, 66 (27%) had stage II AKI, and 118 (48.4%) had stage III AKI. The median time of AKI onset for stage I AKI was 2 days (interquartile range, 1.5-5.5) while stage II and III AKI was 4 days. On multivariable analysis, factors associated with development of AKI were age [subdistribution hazard ratio (SHR) 1.01, 95% confidence interval (CI) 1.00-1.02], SOFA score (SHR 1.16, 95%CI 1.12-1.21), a history of diabetes mellitus (DM) (SHR 1.42, 95%CI 1.07-1.89), and arterial pH on day 1 of ARDS (SHR per 0.1 units decrease was 1.18, 95%CI 1.05-1.32). In severity of AKI, stage I AKI was associated with age (SHR 1.03, 95%CI 1.01-1.05) and serum bicarbonate on day 1 of ARDS (SHR 1.07, 95%CI 1.02-1.13). Stage II AKI was associated with age (SHR 1.03, 95%CI 1.01-1.05), serum bicarbonate on day 1 (SHR 1.12, 95%CI 1.06-1.18), SOFA score (SHR 1.19, 95%CI 1.10-1.30), history of heart failure (SHR 3.71, 95%CI 1.63-8.46), and peak airway pressure (SHR 1.04, 95%CI 1.00-1.07). Stage III AKI was associated with a higher BMI (SHR 1.02, 95%CI 1.00-1.03), a history of DM (SHR 1.79, 95%CI 1.18-2.72), SOFA score (SHR 1.29, 95%CI 1.22-1.36), and arterial pH on day 1 (SHR per 0.1 units decrease was 1.25, 95%CI 1.05-1.49). CONCLUSIONS:Age, a higher severity of illness, a history of diabetes, and acidosis were associated with development of AKI in ARDS patients. Severity of AKI was further associated with BMI, history of heart failure, and peak airway pressure.

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Clinical review: Stem cell therapies for acute lung injury/acute respiratory distress syndrome - hope or hype?

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Clinical review: Stem cell therapies for acute lung injury/acute respiratory distress syndrome - hope or hype?

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