For someone with a severe, incurable lung
disorder such as cystic fibrosis or chronic obstructive pulmonary disease, a
lung transplant may be the only chance for survival. Unfortunately, it’s often
not a very good chance. Matching donor lungs are rare, and many would-be
recipients die waiting for the transplants that could save their lives.
Such deaths could be prevented if it were
possible to use stem cells to grow new lungs or lung tissue. Specialists in the
emerging field of tissue engineering have been hard at work on this for years.
But they’ve been frustrated by the problem of coaxing undifferentiated stem
cells to develop into the specific cell types that populate different locations
in the lung.
Now, researchers from the Univ. of Texas Medical
Branch at Galveston
have demonstrated a potentially revolutionary solution to this problem. As they
describe in an article published electronically ahead of print by the journal Tissue Engineering Part A, they seeded
mouse embryonic stem cells into “acellular” rat lungs—organs whose original
cells had been destroyed by repeated cycles of freezing and thawing and
exposure to detergent.
The result: empty lung-shaped scaffolds of
structural proteins on which the mouse stem cells thrived and differentiated
into new cells appropriate to their specific locations.
“In terms of different cell types, the
lung is probably the most complex of all organs—the cells near the entrance are
very different from those deep in the lung,” said Dr. Joaquin Cortiella, one of
the article’s lead authors. “Our natural matrix generated the same pattern,
with tracheal cells only in the trachea, alveoli-like cells in the alveoli,
pneumocytes only in the distal lung, and definite transition zones between the
bronchi and the alveoli.”
Such “site-specific” cell development has
never been seen before in a natural matrix, said professor Joan Nichols,
another of the paper’s lead authors. The complexity gives the researchers hope
that the concept could be scaled up to produce replacement tissues for humans—or
used to create models to test therapies and diagnostic techniques for a variety
of lung diseases.
“If we can make a good lung
for people, we can also make a good model for injury,” Nichols said. “We can
create a fibrotic lung, or an emphysematous lung, and evaluate what’s happening
with those, what the cells are doing, how well stem cell or other therapy
works. We can see what happens in pneumonia, or what happens when you’ve got a
hemorrhagic fever, or tuberculosis, or hantavirus—all the agents that target
the lung and cause damage in the lung.”
The researchers have already begun work on
large-scale experiments, “decellularizing” pig lungs with an eye toward using
them to produce larger samples of lung tissue that could lead to applications
in humans. They’re also taking on the challenge of vascularization—stimulating
the growth of blood vessels that will enable the engineered tissues to survive
outside the special bioreactors that the researchers now use to keep them alive
by bathing them in a life-sustaining cocktail of nutrients and oxygen.
“People ask us why we’re doing the lung,
because it’s so hard,” Cortiella said. “But the potential is so great, and the
technology is here. It’s going to take time, but I think we’re going to create
a system that works.”
Other authors of the Tissue Engineering Part A paper
(“Influence of Acellular Natural Lung Matrix on Murine Embryonic Stem Cell
Differentiation and Tissue Formation”) are UTMB research associate Jean Niles,
associate professor Gracie Vargas, medical student Sean Winston, graduate
student Shannon Walls, summer research fellows Andrea Brettler and Jennifer
Wang, Andrea Cantu of Stanford University and Dr. Anthony Pham of Brown Medical
School.
SOURCE
