The scientists envisage that one-day 'artery banks' will
become a reality, just like 'blood banks' are today. These artery banks would
be a readily available source of healthy arteries for replacing diseased ones
at the time of surgery. The present research findings take the researchers one
step closer to their goal.
The study, published in Stem
, found a way to
grow smooth muscle cells from pluripotent stem cells
that is superior to
conventional methods. The study has also identified a potential new drug
that can significantly reduce the risk of complications arising during cardiac
The study was led by Dr. James Thomson, PhD,
who is Director of the Regenerative Medicine Laboratory at the Morgridge
Institute for Research, Madison, Wisconsin, USA. The
lead author of the study was Jue Zhang, who is an Associate Scientist at the Morgridge Institute for Research.
"We decided to focus on
blood vessels because cardiovascular disease is a major cause of death
Thomson says. "In the
U.S. for example, heart disease and stroke are the No. 1 and No. 3 killers, respectively.
And this work also has implications beyond making vessels for transplantation;
it's sort of a stepping stone to more advanced tissue engineering."
How Were the Arteries Created in the Lab?
Two essential cell
types are required for the production of arteries in the lab. These are
endothelial cells and smooth muscle cells. The Morgridge researchers in 2017
reported the production and characterization of endothelial cells. The present
study focuses on smooth muscle cells.
In this regard,
Zhang indicated that the growth factors that are conventionally used for
producing smooth muscle cells from stem cells also produce intimal hyperplasia
- a condition in which a part of the arterial wall becomes thickened due to
multiplication and migration of smooth muscle cells, resulting in narrowing of
It should be noted
that intimal hyperplasia is the most common cause of rejection of bypass
grafts. Therefore, the researchers were, naturally, looking for a method that
would reduce the chances of intimal hyperplasia; as otherwise, it would be very
difficult to construct an artery in the lab.
What is the Importance of RepSox?
RepSox is a small molecule identified by the researchers
using high throughput screening (HTS), which has the potential for producing
cells that are capable of contraction. RepSox was identified by screening 4,804
small molecules. In contrast to currently available growth factors, RepSox is
capable of inhibiting intimal hyperplasia and is much more stable than the
former and is also more cost-effective to produce.
RepSox is not only effective for differentiating smooth
muscle cells, but also an ideal drug candidate for inhibiting intimal
hyperplasia that can cause serious complications following bypass surgery
. Moreover, since RepSox is
cell-type specific, it acts on smooth muscle cells without affecting the
neighboring endothelial cells.
Therefore, the stem cell-based HTS technique can be
considered as a novel strategy for the identification of potential new drug
molecules that prevent narrowing of the arteries.
"Even after you have
bypass surgery, you can have some problems with your artery, like restenosis
(narrowing arteries) due to intimal hyperplasia,"
Zhang says. "Currently there are only two FDA-approved
drugs on the market [to address these problems], and they're not cell-type
specific, meaning they have side-effects. We found that RepSox inhibits intimal
hyperplasia and has fewer side-effects."
The study findings have brought the scientists one step
closer to their goal of developing improved treatments for cardiovascular
diseases. However, despite this huge progress, there is still another
challenge, concerning cell maturity.
"Basically this cell
type is better than previous efforts, but it's still not mature yet,"
says. "We need to induce these cells to
become more mature, to be more similar to our native artery, to make it more
- Stem Cell Scientists Clear Another Hurdle in Creating Transplant Arteries - (https://morgridge.org/story/stem-cell-scientists-clear-another-hurdle-in-creating-transplant-arteries/)