Stem Cells Restore Tissue Affected By Acute Lung Injury

Researchers from the University of California San Francisco
presented data today at the ATS 2010 International Conference in New Orleans
demonstrating activity of adult stem cells in treatment of acute lung injury.
This is a common condition in intensive care units that causes respiratory
failure and often leads to death. The cause of acute lung injury is usually
blood borne bacterial infections (sepsis), major trauma, aspiration, or direct
infection of the lung in situations like pneumonia or severe viral infections.
Acute lung injury has a 40% mortality rate and strikes an average of 200,000
patients in the US a year.

In order to study the effects of stem cells in this
condition, human lungs that were not suitable for transplantation were pumped
with blood outside of the body and administered endotoxin, a component from
bacterial walls that causes lung failure in patients with sepsis.

The researchers demonstrated that bone marrow derived
mesenchymal stem cells where capable of preserving lung function and inhibiting
the inflammation when administered to the human lung. Perhaps most important
was the finding that water did not leak into the lung, which is one of the major
causes of respiratory impairment.

"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."

This findings are of particular interest because stem cells
are usually used in the treatment of chronic conditions in which the
administered cells are accelerating/augmenting healing processes that usually
take weeks if not months. In contrast, the therapeutic effects of stem cells in
the context of acute lung injury occur in a matter of hours.

Previously the same research group administered adult stem
cells into the bronchioles of the lung and demonstrate therapeutic effects. The
possibility of injecting stem cells intravenously would possess several
advantages in the treatment of patients that are critically ill, this is because
these patients are usually under mechanical ventilation and the bronchoscopy
procedure may lead to complications.

"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.

He continued "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."

their previous publication the group demonstrated that mesenchymal stem cells
produce the protein keratinocyte growth factor (KGF)-1 which is responsible in
large part for maintaining integrity of the lung. Additionally, they
demonstrated that even administration of proteins made by the mesenchymal stem
cells, without mesenchymal stem cells being in the mix, would also elicit
therapeutic effects.

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