Translational Research:

From the laboratory bench to the patient's bedside, the process of 'translating' ideas, insights, and discoveries generated through basic scientific inquiry to the treatment or prevention of human disease.



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Gaining New Ground
Mesenchymal Stem Cell Administration Doubles Survival in Acute Lung Injury Mouse Model

CHORI scientist Vladimir Serikov, PhD, his colleagues Michael Matthay, MD and Naveen Gupta, PhD at the Cardiovascular Research Institute at UCSF and their team show for the first time that bone marrow-derived mesenchymal stem cells (MSC) significantly improve survival in experimental acute lung injury (ALI) mouse models.

Acute lung injury, also called Acute Respiratory Distress Syndrome is found most commonly in patients being treated in intensive care units (ICUs) for other diseases.

"It's the major leading cause of death in hospital patients," explains Dr. Serikov. "Close to half of all patients who die in the hospital die from adult respiratory distress syndrome."

While ALI remains a significant challenge for ICU physicians, very little ground has been gained in the last 30 years in terms of finding new therapeutic strategies to improve survival. With their novel application of MSC to ALI, however, Drs. Serikov and Gupta, could change all that.

In addition to finding that the intrapulmonary administration of MSC - special adult stem cells that have the potential to develop into a variety of different kinds of cell types - doubled survival rates in ALI mouse models, Dr. Serikov and his colleagues also found comparable histological results.

"Microscopic examination of lung tissue easily detects the presence of immune cells in the lung," Dr. Serikov explains. "The more cells you see in the lung tissue, the pronounced the damage to the lungs is. The histological differences in this case were so pronounced you could see just by the naked eye how much healthier the lungs were of the MSC treated mice."

MSC administration also resulted in a decreased level of pro-inflammatory cytokines, with a concomitant increase in anti-inflammatory cytokines. Because the acute respiratory distress which causes ALI is similar to inflammatory injuries like pneumonia, the balance of pro-inflammatory cytokines and anti-inflammatory cytokines actually determines the outcome of disease.

All of these results suggest that MSC could represent a promising new cornerstone in the treatment of ALI. Although bringing the positive outcomes from this lab study in mice to patient's bedsides in the ICU will take a few steps in between, Drs. Serikov and Matthay are up to the task.

Current studies already underway to test MSC delivery in other clinically relevant models of ALI, such as those related to pneumonia or ventilation injury, and Dr. Serikov hopes to eventually be able to test the efficacy of the method in real patients.

"Once we can confirm that MCS from bone marrow can be applied safely," says Dr. Serikov, "we hope to treat the dozens of ALI patients found every day in the ICUs, with the goal of finally decreasing the mortality in this group of patients."


Monday, May 16, 2011 11:33 PM

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