Scientists have grown
a first-of-its-kind functional heart muscle from stem cells
Mending broken hearts – for real.
Organ transplants are an invaluable way of
saving people's lives when their own organs fail, but organ shortages, waiting
lists, and the powerful drugs required to help recipients' bodies accept their
new parts are just some of the difficulties with existing transplant processes.
But what if there were another way of
replacing organs, one that was less reliant on sourcing whole, living organs
from other people's bodies? Scientists in the US have made progress towards
creating bioengineered human hearts in the lab, by regenerating a functional
human heart muscle. In this case, the procedure still requires using a donated
organ, but one that's fused with cells from the recipient.
The technique involves repopulating a decellularised organ
– stripped of the original donor's living cells – with new cardiac tissue grown
from the potential recipient's induced pluripotent stem cells (iPSCs).
In effect, the donor heart is stripped of the components that would trigger an
immune response from the recipient, and is replaced with the recipients' own
cardiac muscle cells.
"Regenerating a whole heart is most
certainly a long-term goal that is several years away, so we are currently
working on engineering a functional myocardial patch that could replace cardiac
tissue damaged due [to] a heart attack or heart failure," said researcher Jacques Guyette from the
Massachusetts General Hospital Centre for Regenerative Medicine (CRM).
The study, documented in Circulation Research,
was led by CRM surgeon Harald Ott, who previously developed a decellularisation procedure to strip
living cells from rat organs with a detergent solution, before repopulating them
with organ-appropriate grown cells. In the new study, this multi-stage process
has been scaled up and conducted on human hearts for the first time.
Bernhard Jank, MD, Ott Lab, Centre for
Regenerative Medicine, Massachusetts General Hospital
"Generating functional cardiac tissue
involves meeting several challenges," said Guyette. "These include providing a
structural scaffold that is able to support cardiac function, a supply of
specialised cardiac cells, and a supportive environment in which cells can
repopulate the scaffold to form mature tissue capable of handling complex cardiac
functions."
In the study, which drew upon 73 human hearts
authorised for scientific research, the researchers induced pluripotent cells
to differentiate into around 500 million cardiac muscle cells (cardiomyocytes), then seeded them into the
tissue of the decellularised hearts.
After several days in culture, the
cardiomyocytes developed into spontaneously contracting tissue, which the
researchers say represents the first regeneration of human heart muscle from
pluripotent stem cells within a cell-free, human heart matrix. The beating
organs were then mounted in an automator bioreactor system (pictured), which
provides the muscle with a nutrient solution and reproduces certain conditions within
a living heart.
The research might seem a bit grisly – the
team is veering close to Re-Animatorterritory,
after all – but the future applications for healthy, lab-grown organs hold a
huge amount of promise.
"Among the next steps that we are pursuing are improving
methods to generate even more cardiac cells – recellularising a whole heart
would take tens of billions – optimising bioreactor-based culture techniques to
improve the maturation and function of engineered cardiac tissue, and
electronically integrating regenerated tissue to function within the
recipient's heart," said Guyette.