Stem cells restore tissue affected by ALI

May 17, 2010

Human stem cells administered intravenously can restore alveolar epithelial tissue to a normal function in a novel ex vivo perfused human lung after E. coli endotoxin-induced acute lung injury (ALI), according to research from the University of California San Francisco.

The findings will be reported at the ATS 2010 International Conference in New Orleans.

ALI is a common cause of in the intensive care units, often leading to death. It can be caused by both direct injury such as aspiration and pneumonia, and indirect injury such as sepsis and from trauma. ALI is characterized by diffuse bilateral infiltrates on chest x-ray, hypoxemia and both lung endothelial and epithelial injury. Because ALI causes injury to the alveolar epithelium, it impairs its ability to reabsorb fluid from the airspaces of the lung. Yearly, ALI affects approximately 200,000 patients in the US and has a 40 percent mortality rate despite extensive investigations into its causes and pathophysiology. Innovative therapies are desperately needed.

To determine whether given intravenously would be able to repair the damaged alveolar epithelium, researchers used right human lungs that had been declined for transplantation by the Northern California Transplant Donor Network. The lungs were perfused with whole blood and ventilated with continuous positive airway pressure. The researchers then infused the right middle lung with endotoxin, which induces . One hour following injury, clinical grade human mesenchymal stem cells (hMSC)—those that are derived from bone marrow of healthy adults— were given intravenously.

"We found that intravenous infusion of clinical grade cryo-preserved allogeneic hMSC were effective in restoring the capacity of the alveolar epithelium to resolve pulmonary edema when given after the establishment of E. coli endotoxin-induced acute lung injury in an ex vivo perfused human lung preparation," explained Jae-Woo Lee, M.D., who led the study in the laboratory of Michael A. Matthay, M.D. "In addition, we found that intravenous infusion of hMSC preferentially homed to the injured areas of the lung, which means that the cells find their way from the bloodstream to the sites in the lung of injury."

Prior research from the group focused on delivering intrabronchially. Importantly, in this study, the group found that intravenous delivery of hMSC worked as well as intrabronchial administration. Intravenous administration would be preferred in critically ill mechanically ventilated patients with ALI because bronchoscopy may lead to transient problems with oxygenation and ventilation.

In addition to having restored function of alveolar epithelial cells, lungs treated with hMSC showed a reduction in inflammatory cytokine, IL-1 and IL-8, levels suggesting a favorable shift away from a proinflammatory environment in the injured alveolus.

"These results suggest that the intravenous route would be ideal for potential clinical trials of hMSC for severe acute lung injury, a syndrome of acute respiratory failure in critically ill patients that is associated with 40 percent mortality," said Dr. Lee.

"These results extend our recent publication, which demonstrated that hMSC may have therapeutic potential clinically in patients with severe acute lung injury. We need to do more experiments with testing the effect of hMSC against live bacterial induced lung injury in the perfused human lung and now advance to doing Phase I and II safety and efficacy studies in patients."

Explore further: Florida university opens TB lab in Haiti

add to favorites email to friend print save as pdf

Related Stories

Study sheds light on deadly lung disease

Apr 14, 2008

Systemic sclerosis (SSc), also known as scleroderma, is characterized by the formation of fibrosis, or scar tissue, on internal organs as well as the skin. Beyond its disfiguring symptoms, SSc is associated with a high rate ...

Recommended for you

User comments : 0

More news stories

FDA proposes first regulations for e-cigarettes

The federal government wants to prohibit sales of electronic cigarettes to minors and require approval for new products and health warning labels under regulations being proposed by the Food and Drug Administration.

Rising role seen for health education specialists

(HealthDay)—A health education specialist can help family practices implement quality improvement projects with limited additional financial resources, according to an article published in the March/April ...

When things get glassy, molecules go fractal

Colorful church windows, beads on a necklace and many of our favorite plastics share something in common—they all belong to a state of matter known as glasses. School children learn the difference between ...

FCC to propose pay-for-priority Internet standards

The Federal Communications Commission is set to propose new open Internet rules that would allow content companies to pay for faster delivery over the so-called "last mile" connection to people's homes.

SK Hynix posts Q1 surge in net profit

South Korea's SK Hynix Inc said Thursday its first-quarter net profit surged nearly 350 percent from the previous year on a spike in sales of PC memory chips.