Immortality
Update 2
Andre Willers
18 Nov 2013
Synopsis :
Discussion :
2.In Appendix A is a general discussion
.
In Appendix B Dr Loboa has her penny's
worth .
The technique once again is simple .
To the point where super-bandages has
significant effects .
3.Essential points :
- Strip extracellular matrix of cells .
- Seed with body cells.
- Apply growth factors
- Apply tensioning of matrix to steer which type of cells will develop .
4.Athletic injuries .
A star athlete can regenerate damaged
ligaments , knees , muscles .
5.Super athletes .
Slow twitch muscles can be replaced by
long twitch muscles and vice-versa
- Combine this with CRISPR http://andreswhy.blogspot.com/2013/11/crispr-precision-genetic-engineering.html and the techniques in http://andreswhy.blogspot.com/2010/02/beauty-of-genetic-code.html , and we can design cells , use the design with CRISPR to create prototype cells from the host and then grow them using this regeneration technique .
- An interesting problem will be chimaera's created this way . The new organs will be at war with “old” stem cells . What will the immune system do ? Hint : think epigenetic systems .
- Identity : regenerating the brain (or parts of it) .
Oh no ! We know what
happens then . Remember adolescence ? The same , but on growth
factors . Resigned to a second childhood , now we face a second
adolescence . With cougars prowling around .
9.Speed of implementation .
Rich old men are not going to sit
around waiting for FDA approval .
There are six major efforts underway ,
plus all the Universities and Institutes .
Major money , plus long life are the
rewards .
10 . Mind computer interfaces .
Can now be done at high school level
using the techniques above .
11.nD Printing of extracellular
matrix cellular scaffolding. .
Even
a simple 3D printer can print a 4D scaffolding that self-assembles
when coming into contact with a liquid .
Injection
, blood , etc .
12.Singularity :
On track . But the Noosphere expansion
is becoming splotchy , more like the early Universe's microwave
background . Some surfaces are expanding far more rapidly than others
.
The Noosphere is spiking around the
Champions . Expect Singularities there in about 15 years (ie about
2028) . Further Singularities to occur evenly until about 2060 , when
the only Homo Sapiens left will be irredeemable stay-behinds in
reservations . They will be studied and manipulated by intellects
vast , cool and not very sympathetic .
Enjoy the ride .
Andre
xxxxxxxxxxxxxxxxxxxxxxxxxxx
Appendix A
Rebuild
your body
AUTHOR(S)
Coghlan,
Andy
PUB.
DATE
September
2013
SOURCE
New
Scientist;9/14/2013, Vol. 219 Issue 2934, p32
The
article looks at biomedical engineering research into the
regeneration of damaged or diseased tissues and organs with the use
of extracellular matrix cellular scaffolding. The extracellular
matrix contains fibronectin and integrin proteins targeted towards
types of cells, and can promote cell specification by regulating
matrix tension. These properties have been manipulated by biomedical
researchers to grow an artificial kidney, regenerating damaged muscle
tissue, and accelerate bone healing. Also discussed is the
application of extracellular matrix to prevent drug resistant
bacteria wound infection, create vein matrices for kidney dialysis,
and patching fistulas in Crohn's disease.
http://www.smh.com.au/technology/sci-tech/the-body-builders-20131005-2v0yd.htmlSOURABSTRACT
"It
started as a little sore near my knee, probably a mosquito bite,''
says Elizabeth Loboa. But the antibiotic ointment wasn't working, and
within two weeks what was one wound had become three. From the looks
of the wound, her doctor suspected the superbug MRSA and prescribed
powerful last-line oral antibiotics. It was at that point that the
temptation just became too great. ''Instead of taking them, I decided
to test a treatment I'd been developing - on myself,'' she says.
Loboa
wasn't just any patient. In her lab at North Carolina State
University in Raleigh, the materials engineer had been cooking up a
special kind of self-destructing super-bandage capable of healing
infected wounds quickly, without scarring or standard antibiotics.
At
the heart of Loboa's superplaster is a material that degrades until
nothing is left but your own, newly regenerated, healthy cells.
What's more, the same trick could one day be used to heal everything
from shredded muscle and destroyed digestive tissue to shattered
bone. Some researchers have already succeeded in using it to build
entire organs from scratch, and it may one day play a role in
repairing damaged brains. ''It's pretty exciting stuff,'' says
Suchitra Sumitran-Holgersson of Gothenburg University in Sweden.
''We're trying to create a whole new human being.''
Voided:
Scientists used to think the body's matrix just held things together.
Voided:
Scientists used to think the body's matrix just held things together.
So
what is this superstuff? In the body, it is known as the
extracellular matrix - the stuff that remains if you strip away the
living cells from, say, a blood vessel, an organ or a bit of skin.
This scaffolding gives the various parts of our body their detailed
shape and solidity.
And
that's all we used to think it did. ''Everyone thought the matrix
just holds things together,'' says Stephen Badylak, a regenerative
medicine researcher at the University of Pittsburgh in Pennsylvania
who has been one of the early pioneers of matrix-based therapies.
Regenerative medicine researchers had long tried to enlist it to
regrow organs, believing only that it was a useful scaffold. In
animal trials, for example, they would take a kidney and strip it of
native cells using a mild detergent. Then they would use the
remaining inert chassis as a template on which to deposit the
presumed stars of the show: stem cells that recoat the matrix in live
flesh.
But
a few years ago, it became clear that the matrix does a lot more than
it appears. ''Now, we recognise its structure is secondary,'' says
Badylak. ''It's got loads of functional roles.''
Marine
Sergeant Ron Strang, above, has regrown much of the quadricep muscle
he lost in an explosion in Afghanistan.
Marine
Sergeant Ron Strang has regrown much of the quadricep muscle he lost
in an explosion in Afghanistan. Photo: New York Times
For
one thing, the matrix is no biologically mute bystander. While it
consists mainly of inanimate structural proteins such as collagen and
elastin, it also contains proteins that coax the right cells to be in
the right place at the right time. For example, hook-like molecules
called fibronectins and integrins provide tailored molecular Velcro
for specific cells.
Once
these have summoned the right cells, the matrix has another trick up
its sleeve: it can coax them to turn into bone, muscle or fat cells,
according to the tension to which they are subjected once inside the
matrix. In your body, this tension is simply a by-product of the
everyday stresses of muscle movement. In the lab, it is done by
manipulating the stiffness of the matrix. For example, high tension
in the matrix's structure will persuade stem cells to become muscle
or bone. Place them into a saggier matrix and they become fat cells.
Finally,
having convinced them to develop into the right kind of cell, the
matrix also has ways of nourishing them so that they continue to
mature into larger structures. Its material contains potent growth
factors that help blood vessels to form, which provide nourishing
oxygen for the growing organs.
Exploiting
these properties has revolutionised the way we grow organs. Earlier
this year, Harald Ott of Massachusetts General Hospital in Boston
built the world's first functioning artificial kidney, a wildly
complex organ that stem cell researchers have always assumed needed
to be grown from scratch using numerous different cell types. Ott was
astonished to find that although he fed only two types of cells into
a decellularised kidney matrix - blood-like stem cells into the blood
vessels, and endothelial cells into the labyrinthine plumbing that
filters the blood - all the different kinds of cells formed in the
sites where they were supposed to. The kidneys worked so well in rats
that Ott is now using similar techniques to develop hearts, lungs and
pancreases. His is not the only lab pursuing this goal. ''We're
working on livers, hearts, kidneys, oesophaguses, larynxes and small
intestines,'' says Sumitran-Holgersson.
But
organs are not the only things we want to regenerate. Badylak
immediately realised that the matrix's location cues could help him
solve a different problem - growing muscle. Damaged muscle can regrow
to some extent, but if a severe injury destroys too much of one
specific muscle group, scar tissue prevents it from growing back. The
only alternative is transferring muscle from elsewhere in the body,
but that doesn't work very well, says Badylak. Such an injury usually
means amputation and a prosthesis.
But
what if you could use the matrix to attract and grow muscle from a
person's own cells? It would not be the first time: decellularised
tracheas from cadavers have been successfully used in patients to
create new fully working tracheas. So Badylak began a trial in which
he used matrix taken from pig bladder to grow big chunks of muscle in
six people who had lost more than half of a muscle in road accidents
or other trauma. Ron Strang, a 28-year-old US marine whose quadricep
muscle had been destroyed by a roadside bomb in Afghanistan,
volunteered. ''Ron couldn't even get out of a chair without
assistance,'' says Badylak.
After
surgically clearing away all residual scar tissue, Badylak simply
placed a strip of matrix into the exposed void, taking care to make
it taut enough to signal to the body that it should become muscle,
not fat.
The
early results have been astounding. Six months later, the pig matrix
is gone, replaced by a completely new, natural matrix from the
volunteers' own bodies - with muscle to match.
''I
go out hiking,'' Strang says, ''and I'm able to ride a bike.'' He has
also taken up football and basketball. All of the other volunteers
also improved markedly. ''We've got guys mountain-biking who couldn't
stand up before,'' says Badylak. His next goal is to restore at least
25 per cent of lost function to 80 further volunteers.
Building
muscle is one thing. But what about rebuilding shattered bone? That's
what Carmell Therapeutics in Pittsburgh is trying to do, except that
the matrix the company is using is made from human blood. ''Our
material is effectively a highly concentrated blood clot,'' says Alan
West, who runs the company, which is a spinoff from Carnegie Mellon
University. The success of recent animal studies prompted him to
begin a trial in human volunteers.
The
dough-like substance carries high concentrations of growth factors
known to promote bone repair. In a year-long trial in South Africa,
this ''bone putty'' was applied to the broken shin bones, or tibiae,
of 10 volunteers. While West says it is too early to report results,
he hints that the accelerated healing the group has seen should help
them win approval for larger trials, planned in Europe, and work on
other bones.
Superbug
battle
Still,
there are limits to what a natural matrix can do. Loboa, for example,
knew that the natural human extracellular matrix is not naturally
antimicrobial. But she really got to thinking about this problem when
a friend went into the hospital for an ankle replacement and the
wound became infected with MRSA. ''They ended up having to amputate
the leg below the knee,'' she says. It was a wake-up call. ''We're
learning so much about how to regenerate so many different kinds of
tissues,'' she says, ''but how do you keep infection out in the age
of drug-resistant superbugs?''
So
Loboa began to work on a synthetic matrix that could do just that. It
would need to turn slowly into the patient's own tissue without ever
exposing the flesh beneath to microbes. ''The idea is that it's a
bandage that never needs to be changed,'' she says.
Normally,
matrix is harvested from human or pig cadavers. To create her own
version, Loboa began with polylactic acid, a biodegradable material
often used in medical implants, and fashioned it into fibres designed
to mimic the architecture of skin.
''The
novelty is what we can do with these fibres,'' she says. ''We can
make them solid, porous or hollow.'' She chose a porous structure,
which could be impregnated with a cocktail of anti-inflammatory drugs
and Silvadur, a substance containing small amounts of silver ions
that are lethal to most drug-resistant bacteria, including MRSA. The
material works in two phases: the first release overwhelms all
present bugs, and then a second guard leaks out slowly to destroy any
interlopers. The structure dictates how fast the silver ions and
other drugs are released. Loboa tested the silver-seeping matrix in
pigs: even four-centimetre-long wounds injected with MRSA or E. coli
bacteria remained pristine.
And
after seeing it work so many times in her porcine patients, it was
this bandage that she applied to her own wound. And that's when the
true implications hit home. ''I put my scaffold on, and the sores
were gone in three days,'' she says. Soon, the scaffold vanished,
too, leaving at first a dark scar that itself is now nearly gone.
Loboa is about to submit her results for publication, with one
omission. ''I'm not including my leg data,'' she says with a smile.
Synthetic
matrix can also be used as a template to build body parts far
stronger than those nature provides. One group that could benefit
enormously would be the millions of people who undergo kidney
dialysis every year.
Dialysis
is rough on the body: you need to be hooked into machines that
cleanse the blood three times a week, with a large arm vein
punctured. To do a few days of the kidneys' work in a few hours,
blood must be forced through the system at high speed. This heavy use
often makes the veins collapse, so doctors have to continually reopen
them. If all else fails, it is possible to graft veins from other
parts of the body, but during the months it takes for a grafted vein
to mature, a plastic catheterised vein must be inserted that often
gets infected. ''It's harrowing and painful,'' says Laura Niklason, a
tissue engineer at Yale University.
So
Niklason and her colleagues set to work on making customised natural
vein matrix parts that were stronger than the real thing. To do this,
they first crafted a fast-decaying biodegradable polymer into a tube
exactly the dimensions of a vein, but with a thicker vessel wall.
Then they coated this tube with human smooth-muscle cells. Within
days, the cells completely replaced the biodegradable tube with a
matrix of natural collagen, identical to a patient's own - except
thicker and better able to withstand the extra pressures of dialysis.
After decellularisation, these tubes were then surgically implanted
in the patient, and served as the vein for dialysis. Niklason has
plumbed her vein matrices into the arms of 30 volunteers in Poland.
After several months, they are going strong. Niklason has plans for
20 more implants in the US, and is so positive about the vein
matrices that she is hoping they will find a use as coronary bypass
arteries.
That
said, artificial matrix does not have the myriad properties of
natural matrix. Sumitran-Holgersson, who has worked with artificial
materials at Gothenburg University, says that despite the potential
for synthetic implants, natural matrices will always be crucial for
building organs. ''It's definitely superior because it retains so
many important factors to bind and differentiate the cells,'' she
says.
For
some applications, however, it has been possible to create hybrids
that couple the best of both worlds. This provides a promising avenue
to treat one of the worst consequences of Crohn's disease: perianal
fistulas.
These
abscesses eat a channel through the bowel that allows faecal matter
to seep out through the skin or, in the worst cases, into a body
cavity. ''After 20 years with the disease, about 50 per cent of
people will get these,'' says Eugene Boland, who runs Techshot in
Greenville, Indiana, which designs custom medical devices. ''And of
those, 50 per cent will never heal.'' The prognosis is grim, and
untreatable, and includes nappies and constant painkillers.
Working
with the University of Louisville in Kentucky, Boland designed a
matrix-based plug for the fistula. He used polycaprolactone, a
component that, like Loboa's fibres, can be tailored to provide extra
niches for cells. He also added fibrinogen, the component of natural
matrix that aids wound healing.
Brain
rebound
To
emplace them into two people with Crohn's, Boland coated the hybrid
matrix with surface cells derived from their own fat, and implanted
the plugs into fistulas that for years had resisted all treatment. It
worked in both cases. ''They had closed channels after just two
weeks,'' he says. He hopes to treat up to 20 more people before
proceeding to a full trial.
The
matrix holds a dazzling array of future possibilities. Loboa, for
example, is working on a multilayered version that could
simultaneously regenerate multiple kinds of tissue damaged in severe
accidents. Badylak and others are even beginning to explore its
potential for repairing brain damage.
Greg
Bix of Texas A&M University in College Station discovered a key
component of the matrix that could promote brain repair all on its
own: a signalling molecule released from brain matrix that has been
damaged by stroke, called perlecan domain five (DV). It promotes the
growth of new blood vessels. When Bix injected DV into mice and rats
deliberately given strokes, the results were astounding. ''In a
fortnight,'' he says, ''you couldn't tell they'd had strokes.''
It
will be a long time before these treatments become a reality, but
Loboa is hopeful that her idea will generate new treatments for skin
wounds in the not-too-distant future. And even if major artificial
organs are a decade away, as Ott and some of the other researchers
assert, matrix can still help heal more commonplace damage to the
body, such as the muscle, bone and tissue repairs targeted by Badylak
and others.
Even
simple skin wounds are becoming increasingly dangerous as
antibiotic-resistant bacteria thrive in and out of hospitals, and
that is where Loboa's change-free bandage could come into its own.
''Right now, hospitals are scary places,'' Loboa says.
NEW
SCIENTIST
Read
more:
http://www.smh.com.au/technology/sci-tech/the-body-builders-20131005-2v0yd.html#ixzz2l1KBVnCC
Xxxxxxxxxxxxxxxxxxxxxxxxxxxxx
Appendix B
BME’S
LOBOA ANTI-MICROBIAL MATRIX RESEARCH FEATURED IN COVER STORY OF
SEPTEMBER 14 ISSUE OF NEW SCIENTIST
Dr.
Elizabeth Loboa, core faculty in the Joint Department of Biomedical
Engineering, and the work of her Cell Mechanics Laboratory team were
featured prominently in the Cover Story of the September 14, 2013 New
Scientist. The
article (page 33), titled “Rebuild your body,” gives an overview
of the growing use, and importance, of extracellular matrix in
state-of-the-art tissue regeneration. Dr. Loboa’s particular
contribution to this exciting new thrust in tissue healing is a
matrix application that not only promotes regeneration but also
elutes powerful anti-microbial agents capable of suppressing even the
most resistant infectious agents. To see the article by Andy Coghlan
(requires paid subscription) follow this
link: http://www.newscientist.com/article/mg21929340.700-the-matrix-the-secret-to-superhealing-regeneration.html
xxxxxxxxxxxxxxxxxxxx
No comments:
Post a Comment