Researchers at the University of California, San Francisco (UCSF; USA) tested the ability of human allogeneic MSCs in the laboratory to restore epithelial permeability across primary cultures of polarized human alveolar epithelial type II cells, after an inflammatory insult. The cells were grown on a Transwell plate with an air-liquid interface, and subsequently injured by a cytokine combination of interleukin (IL)-1β, tumor necrosis factor (TNF)α, and interferon γ. Protein permeability was measured by albumin flux, which showed a 5-fold increase over the 24 hours that followed the cytokine-induced injury.

The researchers found that when the MSCs were introduced, without direct cell contact, they began to secrete large amounts of angiopoietin-1, which prevented the increase in lung epithelial permeability after the inflammatory injury, in part by preventing stress fiber formation and the suppression of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) activity. The study was published in the August 20, 2010, issue of the Journal of Biological Chemistry.

"Within the past several years, there has been an increased interest in understanding the biology of stem cells for clinical use as cell-based therapies,” said lead author Jae Lee, M.D., an associate professor of anesthesia at UCSF. "We found that these stem cells secreted a significant quantity of a protein that restored the barrier that keeps fluid and other elements out of the lungs. We're optimistic about the promise that future clinical trials may hold.”

Acute lung injury is brought on by a number of conditions, such as pneumonia and sepsis; it may develop into acute respiratory distress syndrome, resulting in insufficient oxygenation of blood and eventual organ failure. The inflammation due to the injury or infection can make the border of epithelial cells become more porous, increasing permeability that allows an often-deadly mix of substances, such as fluid and cells, to seep into and accumulate in the alveoli. Despite extensive research on acute lung injury and acute respiratory distress syndrome, the mortality rate for patients remains high (40%), and pharmacological therapies that reduce the severity of lung injury in experimental studies have not yet translated into effective clinical treatment options.

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