A
new study has inched us closer to designing a new lung with the help of
bioengineering. A team of bioengineers has successfully created a
functional lung with a healthy, perfusable vasculature in an ex vivo
rodent lung.
End-stage lung diseases are the third leading cause
of deaths around the world. It has only one true cure, a lung
transplant. This is not always an option for a majority of the patients
as it is an expensive procedure with a survival rate of just 10% to 12%
after 10 years. Finding a donor's lung is also very difficult and thus,
there is an urgent need for new approaches to saving lives.
Bioengineering a Functional Lung that Breathes
Researchers
around the world are looking for ways to cure lung diseases by
promoting lung repair and increasing the number of donor lungs. However,
lungs are a complex organ with more than 40 different types of cells in
the matrix. The surface area between the airway and the vasculature is
the size of a tennis court. Thus, bioengineering a functional lung from
synthetic or decellularized scaffolds is not an easy task.
Until
now all attempts to create a lung have failed. However, a Columbia
Engineering team led by Gordana Vunjak-Novakovic, University Professor
and the Mikati Foundation Professor at the Columbia University along
with N. Valerio Dorrello, assistant professor of pediatrics at Columbia
University Medical Center have finally tasted success to an extent. They
are the first to successfully bioengineer a functional lung with
perfusable vasculature in an ex vivo rodent lung.
Their study (DOI 10.1126/sciadv.1700521) has been published in Science Advances,
wherein they talk about how their approach allows the removal of
pulmonary epithelium while maintaining the viability and function of the
lung matrix and the vascular network.
The New Approach
The
Columbia team did not follow the traditional approach of building an
organ. Usually, an organ is built from scratch by manufacturing a
synthetic scaffold that resembles the shape of the organ. It is then
seeded with the stem cells or other precursor cells. As lungs are a
complex vascular jungle, most bioengineers have not attempted to build
one. However, the Columbia team generated a natural scaffold by removing
the rat lung cells using detergents. This led to a lung 'skeleton'
consisting of proteins and molecules called extracellular matrix to
remain.
The team in their previous experiments using rat lungs
stripped the epithelial lung cells that are usually damaged in lung
diseases. They also removed the endothelial cells that make up the
vascular system. The team has managed to repopulate the functional
epithelial cells; however, restoration of the blood supply was a
challenge.
The new approach, therefore, attempted to strip only
the lung epithelial cells without disturbing the blood vessels. They
hoped this approach would lead to better results. The researchers tried
an airway-specific method for removal of the pulmonary epithelium. They
even aimed to preserve the lung vasculature, matrix, fibroblasts,
myocytes, chondrocytes, and pericytes.
After the lung cannulation,
they ventilated the lungs and perfused them on an EVLP (ex vivo
perfusion system). Intratracheally, mild detergent solutions were
injected into the isolated lung for removal of the epithelial cells. The
vasculature was protected by circulating a perfusate containing
electrolytes and energy substrates. The result was a lung scaffold that
had a well-maintained bronchial and vascular architecture. The
attachment and growth of human adult, as well as the cell-derived
pulmonary cells in the ex vivo bioreactor, becomes possible due to the
well-preserved architecture.
The building of a functional lung has
become a breakthrough step in the field of bioengineering that has
opened many frontiers in regenerative medicine.
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