Release Subtitle: Researchers use 3D cell culture technology to replicate the pathogenetic process of pulmonary arterial hypertension
Release Summary Text:
Pulmonary arterial hypertension is a rare disease in which excessive
proliferation of the cells of pulmonary arterial walls obstructs the
blood flow in the lungs. A group of scientists based in Okayama, Japan,
has now used 3D cell culture technology to recapitulate the pathogenetic
process involved in pulmonary arterial hypertension in the laboratory,
with potential applications in drug testing.
Full text of release:
Pulmonary arterial hypertension (PAH) is a rare—albeit deadly—disease
that affects the arteries of the lung. In PAH, abnormal growth of cells
of the vascular media—or the elastic wall—of the pulmonary arteries,
called pulmonary arterial smooth muscle cells (PASMCs), results in
thickening of the walls. This leads to the narrowing and/or obstruction
of small pulmonary arteries, thus causing increased pulmonary vascular
resistance and arterial pressure—ultimately leading to right heart
failure. Over the years, various drugs have been approved for PAH
treatment, but the survival of PAH patients three years after diagnosis
still remains at approximately 60%, which is not ideal.
In a recent study published in Frontiers in Bioengineering and
Biotechnology, researchers in Japan, including Professor Mitsunobu R.
Kano and Dr Aiko Ogawa, found a new way to tackle PAH. They reasoned
that to find a solution for PAH, a detailed understanding of the
processes involved in this disease is crucial. To this end, using
three-dimensional (3D) cell culture technology, they established a new
model for PAH “in vitro” (in the laboratory). In this model, they
successfully recapitulated the process central to the pathogenesis and
progression of PAH. Dr Ogawa of the National Hospital Organization
Okayama Medical Center, who led the study, explains, “Given the
importance of vascular medial thickening in the pathogenesis of PAH,
novel therapeutics targeting this process might be beneficial in
improving disease outcomes in PAH patients.” Prof Mitsunobu R. Kano of
Okayama University, who co-supervised the study, adds, “The lack of in
vitro models that recapitulate vascular medial thickening led us to
establish a new model to study this disease.”
The isolation and analysis of PASMCs from patients with PAH have
provided important insights into PAH pathobiology. But, PASMCs are
usually cultured on regular plastic dishes—that is, in two dimensions
only. This precludes the modeling of vascular medial thickening, an
inherently three-dimensional (or 3D) process. Therefore, the scientists
decided to take this method a step—rather a dimension—further. By
applying a “3D cell culture” technique to the PASMCs, they succeeded in
generating an in vitro model of the pulmonary arterial wall with a
thickness comparable to that seen within the human body.
Over the last couple of decades, a key insight that has emerged
regarding PAH pathobiology is that a soluble factor called
platelet-derived growth factor (PDGF) induces the excessive
proliferation of PASMCs. With the new in vitro 3D model of the pulmonary
arterial wall in hand, the team wondered: Could the process of vascular
medial thickening be modeled, if PDGF was applied to the new model?
When the scientists tested this theory experimentally, they indeed found
it to be true. “We found that PDGF induced the proliferation of PASMCs
and increased the thickness of the 3D tissues,” says Prof Kano.
The scientists didn’t stop here: to see whether the model can be used to
assess the ability of particular compounds to suppress vascular medial
thickening, they went on to test the effects of various clinically used
PAH drugs. They observed that treating the model with these drugs led to
changes in the thickness of 3D tissues, which were similar to the
effects of the drugs on PASMC proliferation in the tissues. Therefore,
the scientists realized that their model could not only provide an
important tool in studying PAH but also help to test potential drug
candidates for PAH treatment in the future.
Although there is still a long road ahead, the scientists are optimistic
about their findings. Dr Ogawa concludes, “We plan to use our new model
to enhance our understanding of PAH. We also hope that this novel model
can accelerate the research on PAH pathogenesis and pave the way for
novel treatment strategies.”
Release URL: https://www.eurekalert.org/pub_releases/2020-08/ou-aad080720.php
Reference:
Title of original paper: 3D in vitro Model of Vascular Medial Thickening in Pulmonary Arterial Hypertension
Journal: Frontiers in Bioengineering and Biotechnology
DOI: http://dx.doi.org/10.3389/fbioe.2020.00482
Contact Person: Mitsunobu R. Kano
E-mail: mitkano (a) okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.
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