**1. Introduction**

Sepsis and acute respiratory distress syndrome (ARDS) are life-threatening diseases with high mortality and morbidity in all the critical care units around the world [1–4]. Severe sepsis is a complex syndrome produced by the response to a systemic infection. The infection produces a general inflammatory response, such as tachycardia, elevated white cell count and systemic release of pro-inflammatory cytokines, and this can lead to an acute organ dysfunction. Sepsis is producing more than 5 million deaths per year worldwide [5–8].

The lung is one of the most affected organs during sepsis, and for that reason, one of the main indirect causes of ARDS is sepsis. ARDS can also be produced by a direct injury as a pulmonary infection or a trauma. ARDS is a multifactorial

syndrome characterized by increased lung permeability, hypoxemia, the absence of cardiogenic pulmonary edema, the disruption of the alveolar-capillary barrier, and widespread inflammation. Every year between 1.5 and 4.5 cases per 100,000 inhabitants/year in Europe is detected and in the United States approximately 200,000 new cases are identified per year [1, 5, 8].

There is no definitive therapy that targets the underlying pathobiology of sepsis exists. Nowadays, the treatment is based on antibiotics, infection source control, fluid resuscitation, and organ support [9, 10]. Moreover, several patients die due to secondary infections during the year after the hospital discharge. 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. Nowadays, patients with ARDS have been treated with several ventilator interventions such as lower tidal volumes, higher positive end-expiratory pressure (PEEP), and adjuncts such as prone positioning, neuromuscular blockade, and extracorporeal membrane oxygenation [11–14].

Current advances in the study and knowledge of stem cells have permitted to start using them as a novel treatment for ARDS and sepsis. Based on numerous pre-clinical studies, there is a growing evidence of the potential benefits of cellbased 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 [15, 16].

In animal models, cell therapies have demonstrated noteworthy therapeutic properties including the modulation of the immune system, the release of several factors with growth factor, and antibiotic and anti-inflammatory properties. Cell therapies were tested in several animal models, such as mouse, rat, sheep, and pig models, using several septic and ARDS models. Moreover, different cell types and different administration pathways (intravenously, intraperitoneal, or local administration into the lung) were used as a treatment.

Furthermore, in the last years, a couple of clinical studies started using cell therapies for the treatment of sepsis and ARDS, and some safety and efficient results are published.

This chapter summarizes the different progenitor cells that can be used as a therapy, the mechanisms of action, and the results in pre-clinical and clinical studies in ARDS and in sepsis and future directions.
