First bioartificial heart may signal end of organ shortage
Last Updated: 11:01am GMT 13/01/2008
Breakthrough which marks the creation of the first living artificial
heart could signal the beginning of the end of organ shortages,
reports Roger Highfield
Doctors have stripped down and refurbished a dead heart so that it
can beat once again, marking a world first.
How to grow a heart
Organs to be taken without consent
This unprecedented feat, which marks the creation of the first living
artificial heart, could signal the beginning of the end of organ
shortages.
The revolutionary research could overcome the shortage of replacement
hearts and other organs, and do away with the need for antirejection
drugs, according to an American team.
The world's first beating, retooled "bioartificial heart" is
described today in the journal Nature Medicine by University of
Minnesota researchers in research that could pave the way to a new
treatment for the 22 million people worldwide who live with heart
failure.
The team took a whole heart and removed cells from it. Then, with the
resulting architecture, chambers, valves and the blood vessel
structure intact, repopulated the structure with new cells in a
sterile chamber.
"We just took nature's own building blocks to build a new organ,"
says Dr Harald Ott, a co-investigator who now works at Massachusetts
General Hospital. "When we saw the first contractions we were
speechless."
advertisementThe work has huge implications: "The idea would be to
develop transplantable blood vessels or whole organs that are made
from your own cells," said Prof Doris Taylor, director of the Centre
for Cardiovascular Repair, Minnesota, principal investigator.
The method could be used to grow liver, kidney, lung and pancreas,
indeed "virtually any organ with a blood supply."
She tells The Daily Telegraph that although "years away" from using
the method in hospitals, she is ready to grow a human heart, though
costs make it prohibitive at present.
"We could begin with human cells and pig or human scaffold now but
creating the larger bioreactors (the vessels in which the organs are
grown) and generating the reagents and growing enough cells would
cost tens of thousands of dollars for each heart at this point.
"That is just too expensive to answer basic questions. We of course
want to move in that direction, but funding is limited. As we can we
will go forward - perhaps one heart at a time. "
In general, the supply of donor organs is limited and once a heart is
transplanted, individuals face life-long immunosuppression, where
drugs are used to prevent rejection, often trading heart failure for
high blood pressure, diabetes, and kidney failure over the long term..
Because a new heart created by decellularization could be filled with
the recipient's own stem cells, the parents of other types, the
researchers believe it's much less likely to be rejected by the body.
And once placed in the recipient, in theory the heart would be
nourished, regulated, and regenerated similar to the heart that it
replaced.
"We used immature heart cells in this version, as a proof of concept.
We pretty much figured heart cells in a heart matrix had to work,"
Prof Taylor says. "Going forward, our goal is to use a patient's stem
cells to build a new heart."
As for the source of the cells from a heart patient, she says: "From
muscle, bone marrow, or heart; depending on where the science leads
us."
Although heart repair was the initial goal, decellularization shows
potential to change how scientists think about engineering any organ,
she says. "It opens a door to this notion that you can make any
organ: kidney, liver, lung, pancreas - you name it and we hope we can
make it."
UK Transplant comments that 155 people had their lives saved or
transformed by a heart transplant last year, though 28 died while on
the waiting list. Currently, 81 people are waiting for heart
transplant.
Nationally, more than 9,000 people need a transplant, yet typically
only around 3,000 are performed every year. Last year 1,000 people
died needing a transplant. A UK Transplant spokesman says: "These
developments offer long term hope and long may they continue but the
real problem now is a desperate shortage of donated hearts."
Dr Tim Chico, Consultant Cardiologist, University of Sheffield,
says: "This is an ingenious step towards solving a massive problem.
Heart failure (an inability of the heart to pump sufficient blood,
usually after a heart attack) is increasing in the UK.
"A chronic shortage of donors for heart transplantation makes stem
cell therapy appealing. The study is very preliminary, but it does
show that stem cells can regrow in the 'skeleton' of a donor heart.
However, it will take a lot of further work to assess whether this
will ever be a viable option for patients."
"This very exciting study," comments Dr Jon Frampton, University of
Birmingham. "Although this is only a first step requiring
considerable follow-up development, the study nevertheless represents
an exciting breakthrough that will eventually make the prospect of
repairing damaged hearts a reality and will also be an approach that
can be extended to other organs."
Prof Wayne Morrison, Director of the Bernard O'Brien Institute of
Microsurgery, Melbourne, comments: "This is the first time a whole
organ has been tissue engineered outside the body.
"They have demonstrated that they can create a heart that looks like
a heart and is shaped like a heart and, most excitingly, that they
can re-establish the blood vessels that were originally there. It is
this 'regrowth' of the blood vessel cells that gives the potential in
the future to connect this structure to a blood vessel in the body
and then get circulation to go through it.
Dr Anita Thomas at the Australian Institute for Bioengineering and
Nanotechnology, University of Queensland, adds: "There is one more
major step to achieve before we can proceed any further: we need to
see what happens when these artificial hearts are placed in a
recipient animal for any length of time. The authors of the article
have the necessary skills and yet have not reported their results. We
wait with anticipation for their next publication.
How to grow a heart
While there have been advances in growing heart tissue in the lab,
the problem has been how to create a 3D scaffold that mimics the
complex architecture and intricacies of the body's primary pump.
That is why Prof Doris Taylor and her colleagues resorted
to "decellularization" - removing all of the cells from an organ with
detergent - in this case an animal cadaver heart - leaving only the
extracellular matrix, the framework between the cells, intact, along
with the plumbing and heart valves.
After successfully removing all of the cells from both rat and pig
hearts, the researchers injected rat hearts with a mixture of
immature cells that came from newborn rat hearts and placed the
structure in a sterile chamber in the lab to grow.
The results were very promising, Prof Taylor said. Four days after
seeding the decellularized heart scaffolds with cells, contractions
were observed. Eight days later, the hearts were pumping, albeit at
only two per cent of the efficiency of an adult heart.
A study at of the hearts at the cellular level revealed that
the "cells have many of the markers we associate with the heart and
seem to know how to behave like heart tissue."
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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