|
In the future, if you get in an accident and you lose a kidney, we'll take a skin cell and we'll grow you
up a new one. This is not science fiction.
In the future, tissue engineering and stem cell science will allow us to cure disease, regenerate body
parts, even delay death. Such is the vision of ROBERT LANZA, the chief scientific officer at Advanced Cell
Technology, a Massachusetts biotech firm that is a leader in developing cell-based therapies. The recent
discovery that an engineered virus can restore an adult cell to its youthful condition by altering just a
handful of genes—a technique called cellular reprogramming—brings his futuristic medical goals a bit closer
to reality.
What is so significant about the new technique of cellular reprogramming? You're turning a terminally
differentiated cell back in time to make it what's called an induced pluripotent stem cell. "Pluripotent"
means it can become all the cell types in the body. Induced pluripotent stem cells are not controversial at
all because you don't use embryos or cloning. You can take a skin cell from you, me, or anybody, and then
introduce factors [proteins that initiate DNA transcription] into the cell that will turn it into a
pluripotent cell. You can also introduce the cells into an embryo and they can contribute to the germline
and be passed on to subsequent generations.
How could cell-based therapies help us create and transplant new organs?
The two hurdles for transplantation therapy in the last several decades have always been the shortage of
cells and tissues, and rejection. Embryonic stem cells solve the supply problem, allowing you to generate
an unlimited supply of cells. The problem that has not been solved is rejection, and that's where cloning
or this new technology of cellular re-programming comes in—you are using the patient's own tissue.
What diseases do you expect to see treated with cellular therapies?
We recently published a paper on a type of cell we created called a hemangioblast, which exists only
transiently in the embryo. With the ability to become all of the blood cells-including your immune cells,
red blood cells, all of your blood system, as well as vascu-lature—hemangioblasts have been one of
biology's holy grails. The point is, we can use transient, intermediate cells like hemangioblasts as a
toolbox to fix the adult body so you don't have to amputate limbs from vascular disease, so you may not
have to go blind, or so we can prevent heart attacks. We discovered that you can generate literally
millions, or even billions, of these from human embryonic stem cells. No one had ever done that before.
Then the question was "Okay, this is great. We got a cell in a petri dish. But what does it do? What can it
do?"
Ischemia is what causes people with diabetes to lose limbs—because of the lack of blood, you lose toes,
fingers, everything. Malcolm Moore at Memorial Sloan-Kettering Cancer Center has an animal model of
ischemia. In these animals, if the femoral vein is severed, there is very minimal blood flow, like 10 to 20
percent. We injected hemangioblasts into the muscle of the damaged ischemic limb in a group of these
animals. Within a month we found almost 100 percent restoration of the blood flow. I certainly wouldn't
have expected that. I thought these cells were pretty amazing, but not that amazing.
You are also looking at growing blood from reprogrammed cells, right?
The military is concerned about a real crisis they may face. They don't have enough O-negative blood, the
type that can be accepted by anyone who needs a transfusion. There is often not enough time for tissue
matching in the battlefield environment. In the past they have had severe shortages and have had to fly in
O-negative blood from Germany and other countries. They would like to build a machine they can put on a
Humvee that will make all the blood they want. Now we can make literally 10 to 100 billion red blood cells
from one little six-well plate. We're learning how to make platelets, to be used for clotting, for anyone
in an emergency situation that needs to stop bleeding. That could have tremendous value.
We share the first floor of our building with the American Red Cross. Every day they have their signs out
on the road looking for blood donors: "Urgent need for blood." In a few years, hopefully all they will need
to do is simply say, "Okay, we're running low, make us up 100 units."
Will it be possible to engineer an entire new body part?
To realize the full potential of stem cells, we must learn how to reconstitute them into more complex
tissues and structures. If we want to make an artery or bones or even an entire kidney or a heart, we need
to learn to assemble and grow them on a biodegradable scaffold that the body can later absorb. You let the
cells grow, and when you put them back in the body, the body reabsorbs the synthetic materials that are
biodegradable and you're left only with the living tissue.
In the future, if you get in an accident and you lose a kidney, we'll take a skin cell and we'll grow you
up a new one. This is not science fiction. The field is moving so fast that by the time anyone who is
middle-aged or younger now is older, we will simply grow you a new kidney. What seems like science fiction
and space age is going to become reality really quickly.
What about life span? Will these cells help us live longer?
If you look at the turn of the last century, peopie's life span was, on average, about 36. It is now
double that. It turns out that human longevity plateaus as it approaches around 120 years—that is probably
the maximum. Certainly by eliminating infectious diseases and some of the chronic diseases such as cancer,
we can get over 100. What we're talking about is patching you back together like a bicycle tire up to 120
years. That was always my thinking. But now with these heman-gioblasts, I have questioned my own rules.
These hemangioblasts can go in and fix the damaged tissue.
So, okay, you patch the body together, but then you're going to become senile. Now we're learning that we
may be able to repair the damage in the brain itself, too. If this continues the way it looks like it's
going, we may break that ceiling, like breaking the sound barrier. I'd be very hesitant to put a lid as to
where longevity's going to go.
Article by PAMELA WEINTRAUB from Discover magazine (Summer 2009).
Paralysed rats have been enabled to walk again, by transplanting
nerve cells derived from human embryonic stem cells into the
animals. The findings add to a growing number of studies that
suggest that embryonic stem cells could have a valuable role
to play in treating spinal injuries. The researchers say trials
on people using this technique could start in about two years
time. Researchers are exploring a number of approaches to enable
recovery from spinal-cord injury, including drugs that overcome
spinal cells' reluctance to re-grow, ways of bridging the gap
between severed nerves, and transplants of various tissues,
including adult stem-cells derived from bone marrow, and nerve
cells from the nose. Human trials of some treatments, such
as that using nose cells, have already begun. But the first
stem-call trials will be on patients
with recent spinal cord injuries and localised damage; treating
people who have been paralysed for years, or who suffer from
degenerative nerve diseases, is more difficult.
Ways will also have to be found to prevent people rejecting
the stem cells. One possible alternative to immunosuppressant
drugs would be to first give the patient bone-marrow stem cells
from the same source as the nerve cells. This might trick the
patient’s immune system into developing tolerance.
But adult cells have serious limitations as a mass-market
treatment, because not many cells can be grown from a single
source.
That is not a problem with embryonic stem cells (ESCs). "One
cell bank derived from a single embryo produces enough neurons
to treat 10 million Parkinson's disease patients", says
Thomas Okarma of the Geron company in California. What is
more, adult stem cells may not be as versatile. "At
this moment, there is very little hard evidence that a bone
marrow stem cell can turn into anything but blood, or that
a skin stem cell can become anything but skin", he says.
ESCs, on the other hand, have the potential to develop into
practically any type of tissue.But there is nevertheless
a serious problem with ESCs. "Undifferentiated human
embryonic stem cells have a very high probability of forming
tumours," says Hans Keirstead at the University of California,
Irvine, whose team has performed the latest research. To
prevent this, his team turned ESCs into specialised cells
before transplanting them. They transformed the ESCs into
oligodendrocytes, the cells that form the insulating layer
of myelin that is vital for conducting nerve impulses. Keirstead's
team transplanted the oligodendrocytes into rats with "bruised" spines.
After nine weeks, the rats fully regained the ability to
walk, he says, whereas rats given no therapy remained paralysed.
The team repeated the experiment on three separate occasions,
with the same results. Analysis of the rats' spinal cords
revealed that the transplanted oligodendrocytes had wrapped
themselves around neurons and formed new myelin sheaths.
The transplanted cells also secreted growth factors that
appear to have stimulated the formation of new neurons.While
many promising spinal repair experiments have proved hard
to reproduce, researchers at Johns Hopkins University in
Baltimore, Maryland, also announced similar results last
week. The team injected undifferentiated human ESCs into
rats with injured spinal cords. After 24 weeks, the treated
rats could support their own weight. Team leader Douglas
Kerr thinks the animals' recovery was not due to the growth
of new cells, but to the secretion of two growth factors
(TGF-alpha and BDNF), which protected damaged neurons and
helped them to re-establish connections with other neurons. "The
stem cells' magic was really their ability to get into the
area of injury and snuggle up to those neurons teetering
on the brink of death," says Kerr, whose results will
appear in the Journal of Neuroscience.
"
Umbilical cord blood stem cells are used as a part of the therapy
regimen for nearly 50 diseases today. One of the challenges
in developing additional cellular therapies is the need to
multiply and preserve large quantities of these powerful umbilical
cord blood stem cells for use in treating an even broader range
of diseases. These important studies indicate that we can substantially
increase the number of these valuable cells and freeze them
for later use", says Jan Visser of ViaCell.
Okarma hopes the results will help persuade policy makers
in Washington not to ban therapeutic cloning, which is
one way
of obtaining human ESCs, and increase funding for ESC research. "The
promise of this technology is beginning to be realised",
he says. "That's why we think this battle is worth fighting." |
