Concise review: Mesenchymal stem cells for acute lung injury: role of paracrine soluble factors

Abstract

Morbidity and mortality have declined only modestly in patients with clinical acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), despite extensive research into the pathophysiology. Current treatment remains primarily supportive with lung-protective ventilation and a fluid conservative strategy. Pharmacologic therapies that reduce the severity of lung injury in preclinical models have not yet been translated to effective clinical treatment options. Consequently, further research in translational therapies is needed. Cell-based therapy with mesenchymal stem cells (MSCs) is one attractive new therapeutic approach. MSCs have the capacity to secrete multiple paracrine factors that can regulate endothelial and epithelial permeability, decrease inflammation, enhance tissue repair, and inhibit bacterial growth. This review will focus on recent studies, which support the potential therapeutic use of MSCs in ALI/ARDS, with an emphasis on the role of paracrine soluble factors.

Figure 1

In acute lung injury (ALI), the therapeutic properties of mesenchymal stem cells (MSCs) rely on both paracrine mechanism and through interaction with other cells. Multiple mechanisms have been identified through which MSC therapy may repair the alveolar epithelium and endothelium during ALI, such as (a) secretion of paracrine soluble factor, which restore alveolar fluid clearance, lung permeability, and inhibit bacterial growth, and (b) immunomodulation of innate and adaptive immune cells, which reduce alveolar inflammation. Although not fully characterized, the potential of engraftment by in vivo modified MSCs and the presence of endogenous adult stem cells with characteristics similar to MSCs may also contribute to this therapeutic effect. Abbreviations: Ang-1, angiopoietin-1; IL-10, interleukin-10; KGF, keratinocyte growth factor; MSC, mesenchymal stem cell; PGE₂, prostaglandin E₂; PMN, polymorphonuclear neutrophils.