In a U.S. laboratory, a monkey
arm is stripped down as far as its individual cells. All that's left behind is
a bare, frail scaffold.
But that's not the end of the
road for this arm. The scaffold is rebuilt with infusions of cells from another
being — be it a monkey, or a human — which grow and transform the
limb.
The aim is ultimately to
restore the limb to its fully functional form. But this transformed limb will
contain the blood, bones, muscles, cartilage — and more — not of the
animal it once was, but instead, the animal providing these new cells.
The hope is to eventually use
human cells to make limbs that can be transplanted in humans — and the
technology is already being trialled in monkeys.
Replacing lost limbs
"There are no good
options to replace lost limbs," says Harald Ott, director of the organ
repair and regeneration lab at Massachusetts General Hospital (MGH), in Boston,
who is leading this research.
In the United States, it is
estimated that approximately 185,000 amputations occur each year, and more than
2 million people are currently living with limb loss, according to the Amputee
Coalition.
The current options for
amputees are a diverse range of prosthetics -- incorporating many new forms of
technology to help them feel real -- or transplants, when matching donors are
available. But with these options come limitations in terms of movement and
control. In the case of transplants, the limiting factor is the need for
life-long immunosuppressive drugs to stop a recipient's immune system from
attacking their new limb. Suppressing immunity in this way opens up the risk of
new infections and certain cancers.
Ott's ambitious technique
therefore has an ambitious goal -- to one day provide amputees with fully
functional limbs that can be transplanted as if they were their own.
The idea is to create limbs
made up of cells from the amputee's own body to produce an arm -- or one day
leg -- tailored to them and therefore unlikely to be attacked by their immune
system.
"If it works out you
could regenerate ... on demand," says Ott.
Avoiding immune attack
To date, Ott has managed to
use this technique to grow organs -- including lungs and a beating heart -- and
in June 2015, successfully extended it further to regenerate the arm of a rat
in his lab.
He has now scaled things up --
to monkeys.
To do this, Ott is using what
is known as progenitor cells, which have the ability to differentiate into a
wide range of cell types -- such as blood or muscle cells -- within the body.
They are similar to stem cells but slightly more specialized making them more
easily pushed into creating the specific cells desired by the team.
In their trial on monkeys, the
team are using the scaffold of a monkey's arm but with progenitor cells
obtained from humans and stimulating them into becoming blood cells and
vessels.
"The aim is ... the
formation of a fully lined vascular system," says Ott.
Building body parts
Regenerating a limb is far
from easy, but the complicated process comes down to some key stages, beginning
with finding a limb to regenerate and flushing out all the cells inside with
saline and a sequence of detergents to remove the donor's cells completely.
It's a process known as decellularization and can take up to two weeks to
complete.
"This changes the nature
of the tissue entirely," says Ott referring to the scaffold left when all
possible cells have been stripped.
Next comes the hardest part --
to repopulate the limb with progenitor cells from another individual and guide
them to generate specific cells such as blood vessels, or muscle -- known as
recellularization.
All stages need to happen
inside a tightly controlled environment with set temperatures, humidity, pH,
oxygen levels, and pressure. The regrowth of the arm takes place inside a bioreactor
providing nutrients and stimulation for the limb to reform.
After working with organs, Ott
is preparing to jump the hurdles ahead of him when creating limbs.
"The challenge is their
composite nature ... limbs contain muscles, bone, cartilage, blood vessels,
tendons, ligaments and nerves -- each of which has to be rebuilt and require a
specific supporting structure called the matrix," he says.
After a start with blood cells
and vessels, next comes muscle and then connective tissue, bone, cartilage, fat
cells and more, with the final challenge of nerve cells to make a working arm.
"What's important is to
eventually let that limb become functional again," says Ott.
Rodent success
Ott's success with a rat's arm
was the first bio-limb to ever be created. After weeks of tending to this
miniscule limb, the result was an arm capable of producing blood and muscle
cells and with the ability to contract when electrically stimulated in the lab.
The next challenge is to
create nerve cells and enable them to integrate and work once attached to the
muscle of the animal receiving the new limb. "The nerves need to not only
grow, but re-connect to the muscle," says Ott.
But the success of human hand
transplants in achieving this connection gives Ott some hope. "We've
learned from the transplant community," he says.
Regenerating humans
"[We need] to show we can
apply this process to limbs of human scale," says Ott. In his current work
with Macaque monkeys his team have so far been able to grow the cells of human
vascular tissue and its lining.
And in terms of time, going
bigger doesn't necessarily mean taking longer. "It's a larger field that
you plant with more seeds," says Ott. The formation of a new human limb
should, in theory, take the same amount of time as the rat.
But there's a long road ahead
"It's a very good first
step," says Maximina Yun, a regenerative biology researcher at University
College London. But she adds: "there are still a few challenges to
overcome."
Yun's work on limb
regeneration has focused on the biology of salamanders, which regrow their own
limbs readily when needed. "They can regrow straight after
amputation," she says.
Through her expertise on the
biology of salamanders, Yun hopes to one day apply this knowledge to humans.
She stresses the challenges ahead when growing limbs for humans in terms of
growing nerves in muscles, maintaining their movement and preventing immune
rejection.
"We need a limb that doesn't
pose any risk to humans," she says. Ott agrees and is hopeful he will be
working in science long enough to see his work come to fruition.
"I will live to see the
clinical application of this," he says.
CNN By Meera
Senthilingam
Source: RJ – reviewjournal Posted August 11,
2015 - 3:18pmUpdated August 12, 2015 - 2:41pm
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