Animal Model Of Acute Lung Injury Research Articles

Efficacy of Mesenchymal Stromal Cell Therapy for Acute Lung Injury in Preclinical Animal Models: A Systematic Review.

The Acute Respiratory Distress Syndrome (ARDS) is a devastating clinical condition that is associated with a 30–40% risk of death, and significant long term morbidity for those who survive. Mesenchymal stromal cells (MSC) have emerged as a potential novel treatment as in pre-clinical models they have been shown to modulate inflammation (a major pathophysiological hallmark of ARDS) while enhancing bacterial clearance and reducing organ injury and death. A systematic search of MEDLINE, EMBASE, BIOSIS and Web of Science was performed to identify pre-clinical studies that examined the efficacy MSCs as compared to diseased controls for the treatment of Acute Lung Injury (ALI) (the pre-clinical correlate of human ARDS) on mortality, a clinically relevant outcome. We assessed study quality and pooled results using random effect meta-analysis. A total of 54 publications met our inclusion criteria of which 17 (21 experiments) reported mortality and were included in the meta-analysis. Treatment with MSCs, as compared to controls, significantly decreased the overall odds of death in animals with ALI (Odds Ratio 0.24, 95% Confidence Interval 0.18–0.34, I2 8%). Efficacy was maintained across different types of animal models and means of ALI induction; MSC origin, source, route of administration and preparation; and the clinical relevance of the model (timing of MSC administration, administration of fluids and or antibiotics). Reporting of standard MSC characterization for experiments that used human MSCs and risks of bias was generally poor, and although not statistically significant, a funnel plot analysis for overall mortality suggested the presence of publication bias. The results from our meta-analysis support that MSCs substantially reduce the odds of death in animal models of ALI but important reporting elements were sub optimal and limit the strength of our conclusions.

Lung Transcriptomics during Protective Ventilatory Support in Sepsis-Induced Acute Lung Injury.

Acute lung injury (ALI) is a severe inflammatory process of the lung. The only proven life-saving support is mechanical ventilation (MV) using low tidal volumes (LVT) plus moderate to high levels of positive end-expiratory pressure (PEEP). However, it is currently unknown how they exert the protective effects. To identify the molecular mechanisms modulated by protective MV, this study reports transcriptomic analyses based on microarray and microRNA sequencing in lung tissues from a clinically relevant animal model of sepsis-induced ALI. Sepsis was induced by cecal ligation and puncture (CLP) in male Sprague-Dawley rats. At 24 hours post-CLP, septic animals were randomized to three ventilatory strategies: spontaneous breathing, LVT (6 ml/kg) plus 10 cmH2O PEEP and high tidal volume (HVT, 20 ml/kg) plus 2 cmH2O PEEP. Healthy, non-septic, non-ventilated animals served as controls. After 4 hours of ventilation, lung samples were obtained for histological examination and gene expression analysis using microarray and microRNA sequencing. Validations were assessed using parallel analyses on existing publicly available genome-wide association study findings and transcriptomic human data. The catalogue of deregulated processes differed among experimental groups. The ‘response to microorganisms’ was the most prominent biological process in septic, non-ventilated and in HVT animals. Unexpectedly, the ‘neuron projection morphogenesis’ process was one of the most significantly deregulated in LVT. Further support for the key role of the latter process was obtained by microRNA studies, as four species targeting many of its genes (Mir-27a, Mir-103, Mir-17-5p and Mir-130a) were found deregulated. Additional analyses revealed 'VEGF signaling' as a central underlying response mechanism to all the septic groups (spontaneously breathing or mechanically ventilated). Based on this data, we conclude that a co-deregulation of 'VEGF signaling' along with 'neuron projection morphogenesis', which have been never anticipated in ALI pathogenesis, promotes lung-protective effects of LVT with high levels of PEEP.

MSCs Modified With ACE2 Restore Endothelial Function Following LPS Challenge by Inhibiting the Activation of RAS

Angiotensin (Ang) II plays an important role in the process of endothelial dysfunction in acute lung injury (ALI) and is degraded by angiotensin-converting enzyme2 (ACE2). However, treatments that target ACE2 to injured endothelium and promote endothelial repair of ALI are lacking. Mesenchymal stem cells (MSCs) are capable of homing to the injured site and delivering a protective gene. Our study aimed to evaluate the effects of genetically modified MSCs, which overexpress the ACE2 protein in a sustained manner via a lentiviral vector, on Ang II production in endothelium and in vitro repair of lipopolysaccharide (LPS)-induced endothelial injury. We found that the efficiency of lentiviral vector transduction of MSCs was as high as 97.8% and was well maintained over 30 passages. MSCs modified with ACE2 showed a sustained high expression of ACE2 mRNA and protein. The modified MSCs secreted soluble ACE2 protein into the culture medium, which reduced the concentration of Ang II and increased the production of Ang 1-7. MSCs modified with ACE2 were more effective at restoring endothelial function than were unmodified MSCs, as shown by the enhanced survival of endothelial cells; the downregulated production of inflammatory mediators, including ICAM-1, VCAM-1, TNF-α, and IL-6; reduced paracellular permeability; and increased expression of VE-cadherin. These data demonstrate that MSCs modified to overexpress the ACE2 gene can produce biologically active ACE2 protein over a sustained period of time and have an enhanced ability to promote endothelial repair after LPS challenge. These results encourage further testing of the beneficial effects of ACE2-modified MSCs in an ALI animal model.

Instilled air promotes lipopolysaccharide-induced acute lung injury.

Optimization of intratracheal instillation is necessary to establish an ideal animal model of acute lung injury (ALI) in order to further reveal the cellular and molecular pathogenesis of ALI. It is possible that instilling air from a prefilled syringe may promote the delivery of reagents into the alveolar spaces, resulting in different pulmonary responses. In the present study, the influence of instilling air by trans-tracheal intratracheal instillation in a lipopolysaccharide (LPS)-induced mouse model of ALI was investigated. The bronchoalveolar lavage (BAL) fluid biochemical index, BAL fluid differential cell counts, lung wet/dry weight ratio, lung histology and BAL fluid interleukin-8 (IL-8) levels were assessed 24 h subsequent to intratracheal instillation. Instilled air promoted LPS-induced ALI, as indicated by the severity of acute pulmonary inflammation and increased IL-8 release. In conclusion, this study indicates that instilled air may be used to improve the intratracheal instillation procedure and to establish a more reliable animal model of ALI.

Resolvin D1 reduces deterioration of tight junction proteins by upregulating HO-1 in LPS-induced mice

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is characterized by increased pulmonary permeability with high mortality. Resolvin D1 (RvD1), which has potent anti-inflammatory and pro-resolving activity, can attenuate pulmonary edema in the animal model of ALI. However, the mechanism underlying the protection of RvD1 on pulmonary edema is still unknown. Here we explore the effects and mechanism of RvD1 on the disruption of tight junction protein that results in the permeability edema in a model of lipopolysaccharide (LPS)-induced ALI. The severity of pulmonary edema was assessed by wet-to-dry rate and Evans blue infiltration; expressions of tight junction (TJ) proteins occludin and zona occludin-1 (ZO-1) were examined by immunofluorescence staining and western blot; mRNA in lung tissue was studied by real time-PCR; the TUNEL kit was performed for the detection of apoptosis of pulmonary barrier. Twenty-four hours after LPS inhalation by mice, wet-to-dry rate and Evans blue infiltration indicated that pretreatment with RvD1 relieved the pulmonary edema and pulmonary capillary permeability. Moreover, RvD1 attenuated the LPS-induced deterioration of TJ protein ZO-1 and occludin significantly. And we found that RvD1 increased heme oxygenase-1 (HO-1) expression contributed to the protection on the deterioration of TJs. In addition, we found that RvD1 could reduce pulmonary cellular apoptosis in LPS-induced mice. In conclusion, RvD1 possesses the ability that relieves the pulmonary edema and restores pulmonary capillary permeability and reduces disruption of TJs in LPS-induced ALI of mice, at least in part, by upregulating HO-1 expression.

Novel role for cystic fibrosis transmembrane conductance regulator in alveolar fluid clearance in lipopolysaccharide‐induced acute lung injury in mice

Alveolar fluid clearance (AFC) is important for the resolution of acute lung injury (ALI). The role of cystic fibrosis transmembrane conductance regulator (CFTR) in AFC has not been entirely elucidated in animal models of ALI. The aim of this study was to investigate the role of CFTR and its mechanisms in AFC in normal and ALI mice. Seventy mice were randomly divided into 14 groups and ALI was established by intratracheal instillation of lipopolysaccharide (LPS). After 48 h, CFTR activator CFTRact-16 or inhibitor CFinh-172 with or without β-agonist was instillated intratracheally and AFC was measured with radioisotopic tracer. Although there was no effects of CFTRact-16 on AFC in mice with or without isoproterenol, CFinh-172 markedly decreased isoproterenol-stimulated AFC in both normal (P < 0.01) and LPS-induced ALI mice (P < 0.01) and there was significantly decreased basal AFC in ALI mice (P < 0.05). These results provide direct functional evidence for CFTR in cAMP-mediated AFC in both normal and ALI mice.

Sphingosine-1-phosphate, FTY720, and sphingosine-1-phosphate receptors in the pathobiology of acute lung injury.

Acute lung injury (ALI) attributable to sepsis or mechanical ventilation and subacute lung injury because of ionizing radiation (RILI) share profound increases in vascular permeability as a key element and a common pathway driving increased morbidity and mortality. Unfortunately, despite advances in the understanding of lung pathophysiology, specific therapies do not yet exist for the treatment of ALI or RILI, or for the alleviation of unremitting pulmonary leakage, which serves as a defining feature of the illness. A critical need exists for new mechanistic insights that can lead to novel strategies, biomarkers, and therapies to reduce lung injury. Sphingosine 1-phosphate (S1P) is a naturally occurring bioactive sphingolipid that acts extracellularly via its G protein-coupled S1P1-5 as well as intracellularly on various targets. S1P-mediated cellular responses are regulated by the synthesis of S1P, catalyzed by sphingosine kinases 1 and 2, and by the degradation of S1P mediated by lipid phosphate phosphatases, S1P phosphatases, and S1P lyase. We and others have demonstrated that S1P is a potent angiogenic factor that enhances lung endothelial cell integrity and an inhibitor of vascular permeability and alveolar flooding in preclinical animal models of ALI. In addition to S1P, S1P analogues such as 2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol (FTY720), FTY720 phosphate, and FTY720 phosphonates offer therapeutic potential in murine models of lung injury. This translational review summarizes the roles of S1P, S1P analogues, S1P-metabolizing enzymes, and S1P receptors in the pathophysiology of lung injury, with particular emphasis on the development of potential novel biomarkers and S1P-based therapies for ALI and RILI.

Adult stem cells for acute lung injury: Remaining questions and concerns

Acute lung injury (ALI) or acute respiratory distress syndrome remains a major cause of morbidity and mortality in hospitalized patients. The pathophysiology of ALI involves complex interactions between the inciting event, such as pneumonia, sepsis or aspiration, and the host immune response resulting in lung protein permeability, impaired resolution of pulmonary oedema, an intense inflammatory response in the injured alveolus and hypoxemia. In multiple preclinical studies, adult stem cells have been shown to be therapeutic due to both the ability to mitigate injury and inflammation through paracrine mechanisms and perhaps to regenerate tissue by virtue of their multi-potency. These characteristics have stimulated intensive research efforts to explore the possibility of using stem or progenitor cells for the treatment of lung injury. A variety of stem or progenitor cells have been isolated, characterized and tested experimentally in preclinical animal models of ALI. However, questions remain concerning the optimal dose, route and the adult stem or progenitor cell to use. Here, the current mechanisms underlying the therapeutic effect of stem cells in ALI as well as the questions that will arise as clinical trials for ALI are planned are reviewed.

Cecal Ligation Model of Sepsis in Mice

A large number of small and large animal models of sepsis and acute lung injury (ALI) have been used by investigators for the past four decades. The animal models have been designed to simulate common clinical disorders associated with clinical lung injury, including pneumonia, sepsis (pulmonary or non-pulmonary source), aspiration syndromes (gastric acid, fresh and salt water), and ischemia-reperfusion lung injury (1). A recent workshop provided consensus guidelines for animal models of ALI (2). Nevertheless, most animal models have several limitations because they cannot recapitulate the complex nature of sepsis and ALI in a critically ill patient (3). While mouse models offer some advantages over other animal models because specific mechanisms can be tested with genetic manipulations, it is difficult to measure respiratory and hemodynamic variables on a continuous basis during the course of the experiments and many mouse studies have been limited to shorter term experiments. In contrast, Patel et al (4) recently reported an excellent acid-induced lung injury model in mice studied for 10 days that reflected both the evolution and resolution of ALI, with measurements of extravascular lung water, alveolar fluid clearance, arterial blood gases, biochemical markers of lung injury and lung histology.

58 Effect of Varespladib-Protected Surfactant in Cultured Rat Alveolar Macrophages Stimulated with LPS

BackgroundSecretory phospholipase A2 (sPLA2) is a crucial enzyme for inflammatory response and surfactant catabolism. Acute lung injury (ALI) is a life-threating syndrome characterized by surfactant dysfunction and raised levels of...

Influence of resolvin E1 on inflammatory response in mice with acute lung injury

Objective To evaluate the intluence ot resolvin E1 ( RvE1 ) on intlammatory response in mice with acute lung injury (ALI).Methods The animal model of ALI was established. After 12 h,histological changes,wet-to-dry (W/D) weight ratio of the lungs and the contents of tumor necrosis factorα (TNF-α) in bronchoalveolar lavage fluid (BALF) and nuclear factor-κB (NF-κB) in lung homogenate were observed.Results Histological study showed the lung injury was significantly alleviated in RvE1-treated group.W/D ratio (4.637 ±0.125) g/g and contents of TNF-α (217.2 ±30.1 ) ng/L in BALF of RvE1-treated group were significantly decreased as compared with ALI model group [for W/D ratio:(4.906 ± 0.176) g/g,and for contents of TNF-α:(372.2 ± 20.6) ng/L] ( P ＜ 0.05 ).The level of NF-κB in RvE1-treated group was significantly lower than in ALI model control group.Conclusion RvE1 can inhibit inflammatory response and alleviate lung injury in mice with ALI. Key words: Resolvin E1; Acute lung injury; Inflammatory response; Nuclear factor-κB

Effect of antioxidant in an acute lung injury animal model

The objective of this study was to scrutinize the involvement of nitric oxide (NO) and the diagnosis of blood in ARDS in a rat model determined by the sequential exposure to lipopolysaccharide (LPS). Also, the present study was designed to evaluate the effects of taurine and dexamethasone on ARDS induced by LPS. Measurements of nitrite/nitrate were elevated in BAL of LPS challenged rats, indicative of an induction of the NO synthase. Taurine and dexamethasone abrogated the extent of endotoxin-induced ARDS, as evidenced by the decreases BAL nitrate/nitrite, BALF protein and lung pathology. T+L+D-group had higher PaO2 and lower PaCO2 values than L-group and T+Lgroup. But, ionized Ca2+ and Mg2+ both were not shown significant change. Also, T+L and T+L+D-group showed significant increase compared with L-group, but for the other side no significant difference was seen between T+L and T+L+D group. We suggest that taurine and dexamethasone may be a drug of choice for preventing ARDS.

MicroRNA‐16 regulates ENaC expression in alveolar epithelial cells

ObjectiveMicroRNAs (miRNAs) have emerged as a novel class of gene regulators which play a critical role in complex diseases like acute lung injury (ALI). Our miRNA profiling studies in animal models of ALI revealed that miR‐146a, mir‐16 and miR‐155 were dysregulated. Mir16 targets Serotonin transporter (SERT) which is involved in serotonin uptake. Elevated levels of serotonin in ALI are known to regulate epithelial sodium channel (ENac) expression. The aim of this study is to investigate the functional effects of mir16 on SERT and ENaC in human alveolar epithelial cells (A549) in vitro.MethodsA549 cells were commercially obtained and cultured according to the manufacturer instructions. Cells were transfected with plasmid containing miR16 expressing or control vector by Lipofectamine. q PCR and immunoblot analysis were performed to assess the effects of miR‐16 on SERT, ENaC and other downstream signalling molecules.ResultsA549 cells transfected with miR16 decreased the expression levels of SERT when compared to controls. Dose dependant regulation of SERT was observed in untransfected A549 cells treated with serotonin. Increased expression of ENaC β was observed in miR16 transfected cells compared to controls.ConclusionmiR16 over expression altered SERT and ENaC expression in human alveolar epithelial cells.Research supported by:RO1HL105932(NIH) and 09SDG2260957(AHA)

A mouse model of swine influenza virus H9N2 infection with acute lung injury

BALB/c mice inoculated intranasally with A/swine/HeBei/012/2008/ (H9N2) virus (SIV), showing acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), were observed for morbidity (lung histopathology, lung coefficient, lung wet/dry weight (W/D) ratio, arterial blood gas characteristics and inflammatory cells in bronchial alveolar lavage fluid (BALF)) and mortality. The results showed that, (1) on days 1-4 post infection (p.i.), mice appeared depressed and showed ruffled fur, reduced food intake, weight loss and hypoxemia with a decreased arterial partial oxygen pressure and an increased partial carbon dioxide pressure. (2) From day 4 p.i., mice began to die and showed pulmonary edema, hemorrhage and inflammatory cells in the alveolar exudate. The lung coefficient and lung W/D ratio significantly increased. (3) On days 3-8 p.i., inflammatory cells, especially alveolar macrophages and polymorphonuclears (PMNs) in BALF significantly increased. (4) The mortality rate reached 62.5%. This study established a successful animal model of ALI induced by infection with H9N2 SIV which may help in further investigations of the pathogenesis of human ALI/ARDS induced by H9N2 SIV infection. wine influenza virus; H9N2 subtype; acute lung injury; mouse.

1α,25-Dihydroxyvitamin D3 inhibits neutrophil recruitment in hamster model of acute lung injury

The chemokine interleukin-8 (IL-8) is involved in the pathogenesis of acute lung injury (ALI). Although several studies have reported that 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) suppresses IL-8 production in vitro and in vivo, 1α,25(OH)2D3 has not been demonstrated to be effective in an animal model of ALI. Here, we determined its effects of 1α,25(OH)2D3 in a hamster model where ALI was induced by lipopolysaccharide (LPS) inhalation. 1α,25(OH)2D3 inhibited neutrophil recruitment in the lung by approximately 40% without increasing plasma calcium concentration, while it did not inhibit monocyte recruitment. Our findings show that vitamin D3 analogues may be suitable as novel anti-inflammatory agents for ALI.

Human multipotent stromal cells attenuate lipopolysaccharide-induced acute lung injury in mice via secretion of tumor necrosis factor-α-induced protein 6

IntroductionMultipotent stromal cells (MSCs) are currently in clinical trials for a number of inflammatory diseases. Recent studies have demonstrated the ability of MSCs to attenuate inflammation in rodent models of acute lung injury (ALI) suggesting that MSCs may also be beneficial in treating ALI.MethodsTo better understand how human MSCs (hMSCs) may act in ALI, the lungs of immunocompetent mice were exposed to lipopolysaccharide (LPS) and four hours later bone marrow derived hMSCs were delivered by oropharyngeal aspiration (OA). The effect of hMSCs on lung injury was assessed by measuring the lung wet/dry weight ratio and total protein in bronchoalveolar lavage (BAL) fluid 24 or 48 h after LPS. BAL fluid was also analyzed for the presence of inflammatory cells and cytokine expression by multiplex immunoassay. Microarray analysis of total RNA isolated from treated and untreated lungs was performed to elucidate the mechanism(s) involved in hMSC modulation of lung inflammation.ResultsAdministration of hMSCs significantly reduced the expression of pro-inflammatory cytokines, neutrophil counts and total protein in bronchoalveolar lavage. There was a concomitant reduction in pulmonary edema. The anti-inflammatory effects of hMSCs were not dependent on localization to the lung, as intraperitoneal administration of hMSCs also attenuated LPS-induced inflammation in the lung. Microarray analysis revealed significant induction of tumor necrosis factor (TNF)-α-induced protein 6 (TNFAIP6/TSG-6) expression by hMSCs 12 h after OA delivery to LPS-exposed lungs. Knockdown of TSG-6 expression in hMSCs by RNA interference abrogated most of their anti-inflammatory effects. In addition, intra-pulmonary delivery of recombinant human TSG-6 reduced LPS-induced inflammation in the lung.ConclusionsThese results show that hMSCs recapitulate the observed beneficial effects of rodent MSCs in animal models of ALI and suggest that the anti-inflammatory properties of hMSCs in the lung are explained, at least in part, by activation of hMSCs to secrete TSG-6.

An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals.

Acute lung injury (ALI) is well defined in humans, but there is no agreement as to the main features of acute lung injury in animal models. A Committee was organized to determine the main features that characterize ALI in animal models and to identify the most relevant methods to assess these features. We used a Delphi approach in which a series of questionnaires were distributed to a panel of experts in experimental lung injury. The Committee concluded that the main features of experimental ALI include histological evidence of tissue injury, alteration of the alveolar capillary barrier, presence of an inflammatory response, and evidence of physiological dysfunction; they recommended that, to determine if ALI has occurred, at least three of these four main features of ALI should be present. The Committee also identified key "very relevant" and "somewhat relevant" measurements for each of the main features of ALI and recommended the use of least one "very relevant" measurement and preferably one or two additional separate measurements to determine if a main feature of ALI is present. Finally, the Committee emphasized that not all of the measurements listed can or should be performed in every study, and that measurements not included in the list are by no means "irrelevant." Our list of features and measurements of ALI is intended as a guide for investigators, and ultimately investigators should choose the particular measurements that best suit the experimental questions being addressed as well as take into consideration any unique aspects of the experimental design.

Ultraviolet B light–exposed human platelets mediate acute lung injury in a two‐event mouse model of transfusion

Ultraviolet B (UVB) light has been used alone on platelet (PLT) transfusion products to prevent alloimmunization or with chemical sensitizers to reduce pathogens. Such processing can damage PLTs and potentiate their storage lesion. Transfusion-related acute lung injury (ALI) has occurred in patients whose underlying condition led to an inflamed endothelium and who were transfused with products that contained either HLA or HNA antibodies or biologic modifiers such as lipids or antigens from stored cells. Clinical trials of UV-treated PLTs in patients with thrombocytopenia generated controversy regarding association of these cells with respiratory distress. We evaluated whether UVB PLTs could mediate ALI in an animal model of ALI. We used a two-event animal model where the sensitizing event was lipopolysaccharide (LPS) and the second event was infusion of human PLTs or UVB human PLTs (2.4 J/cm(2) ). Infused human PLTs were followed with whole animal imaging, lung histology, confocal microscopy, lung water, and changes in bronchoalveolar lavage fluid (BALF) related to ALI. In LPS-treated mice UVB human PLTs accumulated in the lungs and were associated with ALI manifested by increased protein and white blood cells (WBCs) in BALF. Untreated human PLTs did not accumulate in the lungs or increase BALF protein or WBC counts. We provide a proof of principle that UVB human PLTs can accumulate in lungs of LPS-primed animals and mediate ALI. PLTs exposed to high doses of UVB could potentially mediate similar effects in patients predisposed with sepsis or other causes of endothelial cell inflammation.

Human models of acute lung injury

Acute lung injury (ALI) is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.

Battling Inflammation in Acute Lung Injury and Acute Respiratory Distress Syndrome: Stem Cell-Based Therapy Targeting the Root Cause of Acute Lung Injury

Acute lung injury (ALI) describes one or more initiating assaults either directly to the lungs or systemically that, if not treated in a timely manner, ultimately progresses to the development of acute respiratory distress syndrome (ARDS) a condition which is characterized by atelectasis, pulmonary hypertension, and an intense, overwhelming inflammatory response that leads to obliterating pulmonary fibrosis and ultimately respiratory failure. The long-term complications associated with ALI/ARDS can be subverted if the fibrotic phase of the disease is suppressed; therefore, it is essential to control inflammation in such a way that endogenous self-protection mechanisms are maintained while not allowing escalating inflammatory damage to occur in the local environment of the lungs. Current treatment strategies focus on optimal ventilator management and treatment of the underlying condition. Cell-based approaches are an attractive option for directed therapeutic intervention for ALI/ARDS. In particular, mesenchymal stem cells (MSCs) from bone marrow, adipose, umbilical cord, and lung tissue as well as induced pluripotent stem (iPS) cells have been shown to facilitate lung repair in several animal models of ALI. The exact mechanism(s) by which these cells accomplish this feat are as yet unknown; however, mounting evidence suggests that they possess potent immunomodulatory and antimicrobial capabilities which diminish the injury-induced inflammatory responses and reduce infection-mediated ALI, respectively, in these various models. Both direct delivery of stem cells to the lung and systemic administration have been somewhat effective, suggesting that stem cells utilize paracrine mechanisms, at least in part, to perform these functions. Aside from their endogenous ability to suppress inflammation and infection, gene-modified MSCs and iPS cells have recently been used as vehicles for carrying anti-inflammatory agents to the lung. Taken together, stem cell therapy is a promising alternative to current therapeutic intervention for ALI/ARDS.