One Sunday lunchtime in March, Anthony Hollander, professor of tissue
engineering at Bristol University, received a call from his colleague Martin
Birchall, a professor of surgery. He had an unusual assignment: they were
being asked to grow a new windpipe for a patient.
“I was having a pub lunch with my family when Martin rang me about this
woman,” said Hollander. “My first reaction was that it was crazy to think we
could put together a plan to save her in just a few weeks. My second was
that it was a chance to prove that what we had been saying for so long was
actually true – that you can use tissue engineering and stem cells to make a
difference to patients’ lives.”
The Bristol team, along with scientists and doctors in Barcelona, Padua and
Milan, set about creating the first tissue-engineered trachea, or windpipe,
using a patient’s own stem cells. These are the “worker” cells that
replenish and rebuild the body’s organs. Claudia Castillo, a 30-year-old
mother of two from Colombia, who was suffering from tuberculosis that would
in time kill her, was to be the recipient.
The team took a donor windpipe from a 51-year-old woman who had died from a
brain haemorrhage and stripped the organ of its cells over six weeks using a
technique called “decellularisation” developed at Padua University. The
scientists were left with a bare “scaffold” of the windpipe.
While the donor trachea was being stripped, the Bristol team obtained stem
cells from Castillo’s bone marrow and made them multiply. The cells were
then persuaded to develop into cartilage cells, a process which took three
weeks.
At the beginning of June, the whole enterprise almost fell apart at Bristol
airport when the British team tried to transport the cells to Barcelona,
where the operation was to take place. EasyJet, the budget airline, would
not allow the surgical team to travel with the precious package.
The timing was critical as the cells could survive for only 16 hours outside
laboratory conditions and one of those had already passed. Birchall became
so irate that he was nearly arrested.
Fortunately, one of his colleagues remembered a doctor with a pilot’s licence
he had known as a student – five minutes and three telephone calls later
they had found a plane in Germany and another doctor who was able to drop
everything, fly to Bristol and on to Barcelona.
“It cost £14,000,” said Birchall. “I was going to try to put the cost of the
plane on my credit card, but luckily the university vice-chancellor stepped
in.”
In Barcelona, the cells were seeded onto the scaffold and grew into place over
four days. The operation took place on June 12 at the Hospital Clinic of
Barcelona, led by Professor Paolo Macchiarini. It was a complete success.
“Just four days after transplantation the graft was almost indistinguishable
from adjacent normal bronchi,” said Macchiarini. Using Castillo’s own stem
cells meant that her body recognised the transplanted trachea as her own and
did not reject it, a common problem with transplant surgery.
Five months on she is able to care for her two children, walk up two flights
of stairs and, occasionally, go out dancing in the evenings.
While the operation has transformed Castillo’s life, it also marked a new era
in medicine. Laboratory-grown hearts, lungs, livers and kidneys and the
regeneration of brain tissue, previously the stuff of science fiction, are
now within sight.
“Surgeons can start to see and understand the very real potential for adult
stem cells and tissue engineering to radically improve their ability to
treat patients with serious diseases,” said Birchall.
“We believe this success has proved that we are on the verge of a new age in
surgical care.”
Stem cell transplants from bone marrow have been used for decades in cancer
patients to replace cells in their own bone marrow that have been killed off
by chemotherapy or radiotherapy.
More recently, however, scientists have realised the potential of the stem
cells to be manipulated in the laboratory to become any other cell in the
body. If the patient’s own stem cells are used, as in Castillo’s case, there
is no need for immuno-suppressive drugs to be administered because they are
not rejected by the immune system. These drugs have been linked to a high
incidence of cancers in transplant patients.
Progress in the field has been rapid. Stem cells are used to grow replacement
skin, which aids wound healing, and Dr Anthony Atala, of the Institute for
Regenerative Medicine at Wake Forest University in North Carolina, has made
and successfully implanted segments of bladder in seven patients, aged
between four and 19, who had birth defects.
Hollander and his colleagues have even grown a “living bandage” from a
patient’s own stem cells to heal tears to the meniscal cartilage in the
knee, a common sporting injury.
Castillo’s operation gives hope to researchers looking at the transplant of
bigger organs. Scientists believe that over the next five years they will be
able to grow a larynx from a patient’s own stem cells while colons, livers
and hearts will be routine within 20 years. They are also researching the
use of stem cells from embryos to grow nerve cells to treat brain diseases
such as Alzheimer’s and Parkinson’s. The possibilities extend to almost
every organ in the body (see panel).
Britain’s Medical Research Council (MRC) is funding projects using stem cells
to treat muscular sclerosis, strokes, retinal damage and hip and other forms
of bone repair.
“In terms of clinical impact within the next couple of years the next big
development from this work is likely to be using embryonic stem cells to
treat macular degeneration – age-related blindness, which affects huge
numbers of people,” said Rob Buckle, the MRC’s head of stem cell and
regenerative medicine research. “Bone and cartilage repairs will be the
next. Using adult stem cells you would embed stem cells in a replacement hip
joint to get a better repair. With heart and liver repairs we are looking at
a longer term of five years or so before treatment becomes available.”
There has been controversy about the MRC’s allocation of more than 50% of its
£23.6m funding to work using embryonic stem cells, with the remainder being
used on adult stem cells.
Some scientists believe that it is more ethical to use adult stem cells, as
research work on cells from human embryos destroys the embryo. They also say
it may even be unnecessary, given that so much progress has been made with
stem cells that are readily available in our bodies.
Such debate will become even more heated as stem cell research delves further
into the realms of science fiction. Scientists are already working on
creating sperm from stem cells taken from bone marrow and embryos. Karim
Nayernia, professor of stem cell biology at Newcastle University, has grown
sperm cells, which later go on to create sperm, from bone marrow.
Manufacturing sperm in the laboratory would be welcomed as a treatment for
male fertility. However, there are concerns that the technique could make
men redundant.
Once sperm, and even eggs, are grown from stem cells in the laboratory,
reproduction could be changed completely without the need for biological
mothers or fathers – which would create a whole new era for our species and
not just for medicine.
