Potential application of mesenchymal stem cells in acute lung injury

Abstract

Despite extensive research into the pathogenesis of acute lung injury and the acute respiratory distress syndrome (ALI/ARDS), mortality remains high at approximately 40%. Current treatment is primarily supportive, with lung-protective ventilation and a fluid conservative strategy. Pharmacologic therapies that reduce the severity of lung injury in experimental studies have not yet been translated into effective clinical treatment options. Therefore, innovative therapies are needed. Recent studies have suggested that bone-marrow-derived multipotent mesenchymal stem cells (MSC) may have therapeutic applications in multiple clinical disorders including myocardial infarction, diabetes, sepsis, hepatic and acute renal failure. Recently, MSC have been studied in several in vivo models of lung disease. This review focuses on first describing the existing experimental literature that has tested the use of MSC in models of ALI/ARDS, and then the potential mechanisms underlying their therapeutic use with an emphasis on secreted paracrine soluble factors. The review concludes with a discussion of future research directions required for potential clinical trials.

Therapeutic Potential of Mesenchymal Stem Cells for Severe Acute Lung Injury

“…1 In acute renal failure in mice, IV MSC therapy hastened renal tubular epithelial recovery. 9 IV MSC markedly improved mortality from peritoneal sepsis in mice, an effect that was explained by the release of PGE 2 from the MSC, which reprogrammed alveolar macrophages to increase production of interleukin (IL)-10.…”

“…MSC do home to injured organs, whether the injury occurs in the liver, kidney, or the lung. 1 The effi cacy of the IV vs the intraalveolar route is being tested in our ex vivo perfused human lung preparation and in small animal models of ALI. Preliminary evidence indicates that the IV route is as effective as the intraalveolar route.…”

Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes

“…IN THE PAST DECADE, cellular therapy with mesenchymal stem cells (MSC) has been tested in several models of organ injury (17,22). MSC were used first in a clinical trial of osteogenesis imperfecta (15), then in lysosomal storage disease (18), and subsequently in graft vs. host disease (20).…”

Stem cell manipulation, gene therapy and the risk of cancer stem cell emergence

“…At the functional level, the fact that MSCs can differentiate into bone, cartilage and fat under appropriate stimulatory conditions, represents the major critical requirement to identify putative MSCs population in vitro. Moreover, under certain culture conditions, they can differentiate into dopaminergic neurons, pancreas, cardiac and lung cells, astrocytes and endothelial cells (56,(58)(59)(60).…”