Researchers
in Oxford and California experiment with medical technology that could make
transplants unnecessary
 |
Embryonic cells under the microscope. Scientists on both sides of the Atlantic
are working on ways of adapting cells to help repair damage from heart attack.
Photograph: Mauricio Lima/AFP/Getty Images |
Every two
minutes someone in the UK has a heart attack. Every six minutes, someone dies
from heart failure. During an attack, the heart remodels itself and dilates
around the site of the injury to try to compensate, but these repairs are
rarely effective. If the attack does not kill you, heart failure later
frequently will.
Transplants
have their own problems – successful operations require patients to remain on
toxic, immune-suppressing drugs for life and their subsequent life expectancies
are not usually longer than 20 years.
The
solution, emerging from the laboratories of several groups of scientists around
the world, is to work out how to rebuild damaged hearts. Their weapons of
choice are reprogrammed stem cells.
These
researchers have rejected the more traditional path of cell therapy that you
may have read about over the past decade of hope around stem cells – the idea
that stem cells could be used to create batches of functioning tissue (heart or
brain or whatever else) for transplant into the damaged part of the body.
Instead, these scientists are trying to understand what the chemical and
genetic switches are that turn something into a heart cell or muscle cell.
Using that information, they hope to programme cells at will, and help the body
make repairs.
It is an
exciting time for a technology that no one thought possible a few years ago. In
2007, Shinya Yamanaka showed it was possible to turn adult skin cells into
embryonic-like stem cells, called induced pluripotent stem cells (iPSCs), using
just a few chemical factors. His technique radically advanced stem cell
biology, sweeping aside years of blockages due to the ethical objections about
using stem cells from embryos. He won the Nobel prize in physiology or medicine
for his work in October. Researchers have taken this a step further – directly
turning one mature cell type to another without going through a stem cell
phase.
At Oxford,
Riley has spent almost a year setting up a £2.5m lab, funded as part of the
British Heart Foundation's Mending Broken Hearts appeal, to work out how to get
heart muscle to repair itself. The idea is to expand the scope of the work that
got Riley into the headlines last year after a high-profile paper published in the journal Nature in which he showed a means of repairing cells damaged during
a heart attack in mice. That work involved in effect turning the clock back in
a layer of cells on the outside of the heart, called the epicardium, making
adult cells think they were embryos again and thereby restarting their ability
to repair.
During the
development of the embryo, the epicardium turns into the many types of cells
seen in the heart and surrounding blood vessels. After the baby is born this
layer of cells loses its ability to transform. By infusing the epicardium with
the protein thymosin β4
(Tβ4), Riley's team
found the once-dormant layer of cells was able to produce new, functioning
heart cells. Overall, the treatment led to a 25% improvement in the mouse
heart's ability to pump blood after a month compared with mice that had not
received the treatment.
Riley says
finding ways to replace damaged cells via transplantation, the dominant
research idea for more than a decade, has faltered. Scientists have tried out a
variety of adult stem cells – derived from areas such as bone marrow, muscle
and fat – turned them into heart cells and transplanted them into animal
models, which initially showed good results.
But those
results could never be repeated in humans with the same degree of success.
"In humans, moving into clinical trials, the actual benefit, from a
meta-analysis just on bone-marrow-derived cells, is a meagre 3%
improvement," he says. "That's barely detectable clinically and
unfortunately isn't going to make a vast amount of difference to your overall
quality of life."
The
original impression from rodent studies was that the transplanted cells would
become new muscle and contribute to improving damaged areas, but Riley says
that idea has fallen out of favour. "All they do, if anything at all, is
to secrete factors that will help the heart sustain the injury, rather than
necessarily offer long-term regeneration."
That is
where the reprogrammers get going. Find the chemical factors that will make a
cell (a skin cell, say, or a piece of scar tissue) think it is in the womb, so
it switches certain genes on and others off and becomes a new heart cell, and
you can avoid the large-scale transplant altogether. All you need is an
infusion of the right drugs and resident cells will do all the required repair
work.
The process
requires an understanding of how an embryo develops and what cues nature uses
to grow all the body's cell types from just a sperm and an egg. This ability to
regenerate does not quite stop at birth: injure a one-day-old mouse's heart,
for example, and it will completely regenerate. Injure it again after a week
and the heart will scar. "Within seven days, it goes from completely
repairable to the adult wound-healing default position," says Riley. "We
want to understand what happens during that window."
Though his
work is yet to be published in a peer-reviewed journal, Villeda speculated the
young blood was likely to be working in the older mice by increasing levels of
chemical factors that tend to decline as animals get older. Bring these back,
he says, and "all of a sudden you have all of these plasticity and
learning and memory-related genes that are coming back".
"We've
redeployed nature's own toolkit in these cells to convert non-muscle cells that
are in the heart into new muscle. More than half of the cells in the heart are
not muscle [but] architectural cells called fibroblasts that are meant to
support the muscle," he says.
"We
had the idea that if we could somehow fool those cells into thinking that they
should become muscle, then we have a vast reservoir of cells that already exist
within the organ that might be able to be called upon to regenerate the heart
from within."
He injected
three chemical factors – called Gata4, Mef2c and Tbx5, collectively known as
GMT – into the damaged region of a heart and, within a month, the non-beating
cells that normally ended up becoming scar tissue had become functioning heart
cells that had integrated with their neighbours. "The factors get taken up
by the fibroblasts and the non-muscle population of cells and they initiate a
genome-wide switch of the programme of the cells so that it now begins to
activate thousands of muscle-specific genes and it turns off thousands of
fibroblast genes."
Srivastava
directs cardiovascular and stem cell research at Gladstone, the institute where
Yamanaka carried out his Nobel-prize-winning work. Srivastava's direct
reprogramming technique takes Yamanaka's work further because it allows
scientists to turn one type of cell into another without having to go through a
stem cell phase in between, thus reducing the risk that any future therapy
might induce cancer.
The method
has been proven to work, so far only in Petri dishes, for blood, liver and
brain cells. "Ultimately, as we learn enough about each cell type, it's
likely we might be able to make most cell types in the body with this direct
reprogramming approach," he says.
The tough
task for all these scientists – from those working specifically on the heart
such as Riley to those working more generally on all cell types such as
Srivastava – is to identify and catalogue the thousands of chemical factors
that are at work in the various stages of cell development, and that are the
keys to the transformation of one cell into another. Riley's team is working
with Shoumo Bhattacharya at the BHF Centre for Cardiovascular Target Discovery
at Oxford, led by Shoumo Bhattacharya, to screen thousands of small molecules
in the lab that could, in combination or isolation, predict a certain type of
cell behaviour in a living heart.
Meanwhile,
the Gladstone team have started experimenting with their direct reprogramming
technique in pigs, as a preclinical trial before trying it out in humans.
"We're trying to do the same experiments we did in the heart in the pig's
heart because it is very similar in size and physiology to human hearts. If it
works there and it is safe, then we'd be ready for a human clinical
trial," says Srivastava.
He has not
entirely abandoned investigating cell transplantation, using muscle cells
derived from embryonic stem cells. But he is clear which would make the simpler
therapy.
"We're
testing both head to head – let's say both works, then I think the direct
reprogramming method will be a lot easier."
And the
relative simplicity of direct reprogramming, discovered by Yamanaka just five
years ago, still surprises him. "It's phenomenal," he says. "We
never thought it would be this way."
"The Quantum Factor" – Apr 10, 2011 (Kryon channeled by Lee Carroll) (Subjects: Galaxies, Universe, Intelligent design, Benevolent design, Aliens, Nikola Tesla (Quantum energy), Inter-Planetary Travel, DNA, Genes, Stem Cells, Cells, Rejuvenation, Shift of Human Consciousness, Spontaneous Remission,
Religion, Dictators, Africa, China, Nuclear Power, Sustainable Development, Animals, Global Unity.. etc.) - (Text Version)
"..... Cell Division - a Static process ?
Let me take
you to the cellular division process. We've said this before, but you need to
hear this to understand how it works. A cell is ready to divide. The Human body
is designed to rejuvenate... all tissue. You've been told that there's some
tissue that does not rejuvenate, but that is incorrect. It all rejuvenates at different
speeds at different times and in different ways. It rejuvenates. So now you
know that the Human body is designed to live a long time. Unfortunately, the
energy that you have created on this planet and what you've gone through, has
beat it up. You don't live much more than 80 years. That was not the design.
The
Biblical personalities were sometimes prophets and sometimes masters and
sometimes just there... and lived for hundreds of years. Did they really? Or
perhaps this is that just a metaphor? Did they get that right in the Bible
without a error in transcription? I'm going to tell you the truth. It's very
accurate. Thousands of years ago you lived a very long time, Lemurian. If you
knew your lifespan, you'd gasp. But not anymore. Instructions have been given
over time to DNA, literally, by the energy of the planet... en energy that you
have created through consciousness.
A cell
divides. Right before it divides, it needs the blueprint to clone itself. The
blueprint is available from the stem cell. The stem cell gets its information
from the quantum part of the DNA, which has never changed since you were born.
It's remained static, since nothing has ever changed it... and the fact that
you don't believe it's changeable and have just accepted aging. There's not a
conscious effort to do anything with it, and it just lays there like it always
did.
The diving
cell "talks" to the stem cell and says, "Do the same thing you
always did? Change anything?" And the stem cell talks to the cell that is
dividing, saying, "Make another one just the same." Then you
rejuvenate just like the last one, accepting everything you received when you
were born. ..."
"Recalibration of Knowledge" – Jan 14, 2012 (Kryon channelled by Lee Carroll) - (Subjects: Channelling, God-Creator, Benevolent Design, New Energy, Shift of Human Consciousness, (Old) Souls, Reincarnation, Gaia, Old Energies (Africa,Terrorists, Cuba, Iran, North Korea, Venezuela ... ), Weather, Rejuvenation, Akash, Nicolas Tesla / Einstein, Cold Fusion, Magnetics, Lemuria, Atomic Structure (Electrons, Particles, Polarity, Self Balancing, Magnetism, Higgs Boson), Entanglement, "Life is necessary for a Universe to exist and not the other way around", DNA, Humans (Baby getting ready, First Breath, Stem Cells, Embryonic Stem Cells, Rejuvenation), Global Unity, ... etc.) - (Text Version)
”… There are several things that are going to happen in mainstream science. First, you're going to find some secrets of DNA and they're going to be embryonic. Start watching scientists discover the embryonic cells and the magic within them. You already know that unusual stem cells exist in the placenta. You also know that the pre-programmed adult stem cells are still there in the body. But what about the DNA of the unborn? (Intellectuals, please keep reading, for to stop now will create unrest.) Second, your work today Yawee, will represent "the perfect template" without using what you did in Lemuria. That's why you're the Human who will do this. It's an extension of why you came here, and is perfect for 2012 and beyond.
These embryonic cells of the unborn are untouchable by society, and they might as well be on Mars, for no science is going to try to use these cells in a 3D manner, which is all you know how to do at this point. If they try, it won't work anyway. There are quantum processes you are learning about that are not only non-invasive, but actually helpful and that can transfer attributes from one biological cell to another and from one Human to another. Think "wireless" [Kryon human again]. What you thought would take wires over 1,000 miles long is now done with satellites. It's an analogy that shows you that you are moving into totally new understandings of the transfer of energy. Let's discuss the mother in that temple for a moment. …”
"... I want to define life for you - not biological life, but spiritual life. So for all those intellectuals, just hold on, for many won't like this. Spiritual life, as measured by Spirit, is when a Human has free choice. When is that? It's when they take their first breath. Not in utero. There will be those who will say, "That's wrong, that's wrong. The soul in the woman's body is alive!" Just wait. I'm talking about spiritually. That which Spirit sees, and it's when you come from the other side of the veil and take your first breath.
A child with the mother has no free choice. That child is linked to the choice of the mother until it is born. It is, indeed, a soul in preparation for free choice, and there are many attributes that are spiritual that we have discussed before about how that soul reacts. But now I'm discussing life with polarity [duality], free choice.
But let's discuss that "child inside" for a moment, for there is a process I want you to know about. I want to talk about 240 days into the pregnancy. At about that time, the child has perfect DNA. It hasn't taken its first breath. The DNA hasn't measured the energy of the planet yet, since it is contained. Did you realize that? Inside the womb is a perfect child. The child's DNA has all the attributes of the Akash and also the parent, but it's different in a way you have not been told. The DNA is 100% as designed.
The quantum instructions within the DNA are all talking to the biology of the child,, getting ready for the first breath. ..."
