Cord of life

-- THE role of the umbilical cord as a foetus's lifeline does not end with birth.
Researchers in the us and Europe now
say that the cord blood can provide a
new lease of life to siblings suffering
from potentially fatal diseases like
leukaemia and even AlDs and also from
disorders such as diabetes and rheumatoid arthritis.

The umbilical cord, which is
removed and discarded after delivery,
contains a large number of stem cells
- cells that can give rise to indefi-
nitely more cells of the same type, and
from which certain other kinds of cells
arise by differentiation - bearing the
co34 cell marker, which is normally
found in bone marrow. Because of
the stein cells, the cord blood can prove
especially useful in treating blood
disorders like icukaemia (Science, Vol 268, No 5212).

Other, advantages of cord blood
include the possibility of indefinite storage, and transplanting it
back to its original owner
when required. It can also be donated to an unrelated
recipient because it has reduced immunoreactivity, which lowers the chance of
rejection by the recipient's immune systent or even of devastating side-effects
like graft-versus-host disease (GVHD).
Till date, 75 cord blood transplants have
taken plaGe all over the world, and cord
blood banks are springing up in medical
centres across Europe and the us.

If cord stem cells can reconstitute
bone marrow Cells, then they can also be
used in gene therapy, conclude some
optimistic scientists. Theoretically, if a gene is added to the cord
blood cells before trans can plantation, then it should
new be expressed in every blood cell. 'I think the
to application of cord blood
to the clinic is going to be
much larger for gene their
apy than for strict transplants or malignant disease," says haematologist
David Harris of the University of Arizona,
and Tucson.

But John Barrett, head
of the bone marrow transplant unit at the National
Heart, Lung and Blood Institute in
Bethesda, Maryland, is not quite sure of
the claims of reduced Gvin). He concedes
that cord blood therapy is'a'good idea,'
but adds that 'I'm a bit skeptical.

Cord blood cells contain more CD34
cells than adult blood because the foetus
generates large quantities Of CD34s in its
liver and bone marrow during its development. Cord blood cells have a "greater
proliferative capacity" than the cells in
the bone marrow, and this gives it an
edge over bone marrow.

Says haematcdogist David Linch
University College London, "Bone
row is rather a waste, You could th
most of it away, as all you are really
is the primitive stem cells that have.1
the self-renewal capacity and the
city to re-populate and produce ma
blood cells."
The exact mechanism for the
decreased immune reactivity is not yet
kown. one of the reasons could be that
cord blood cells have a muted immune
system and its T-cells, which attack specific antigens, are rather 'naive'. Says Eliane Gluckman from Hopital St Louis in Paris,
where the first cord blood transplant was
tried out, "It could be that the naive T-cells
are more tolerant, or there may be a suppressive effect by the maternal cells still floating in the cord blood."

Gene therapy
The first attempt at gene therapy through
d blood was made by Donald Kohn of
Children's Hospital in Los Angeles in
spring of 1993. His aim was to intror a missing gene into 3 children suffer from adermsine deammase (ADA) defiicy, a potentially fatal defect which can
cipple the immune system. CD34 cells
were separated from each child's cord
blood just after birth. Then Kohn's team
used a retrovirus to carry the ADA gene into
the CD34 cells, which were then reintroduced into the children when they were
A 23-month follow up shows the criment to be partially successful so
The gene is expressed in about 1 per
t of the bone marrow population and
vienger RNA (ribonucleic acid) for the
yme is being produced, thus proving
the gene is being expressed. With the
c being expressed in only I per cent of
stem cells, Kohn now wants to concentrate on optimising the number of cells
with the gene.

Among the many proposed therapies,
The most ambitious is the one proposed by
Anthony Ho and Flossie Wong-Staal of
The University of California, San Diego,
who wish to me Kohn's technique to treat
children with AIDS. Stem cells are not
infected by HIV, so the researchers hope to
extract CD34 cells from the cord blood of
babies born to HIV-POSitiVe mothers and
insert into those cells an anti-mv gene -
for an enzyme that can cleave HIV RNA.

Once this gene is expressed, it would
inhabit Me reproduction in the child's
cells.Clinical trials are scheduled to start
early next year.

Though a lot of scientific scrutiny is
sired for exploring the full potential of
cord blood, enough evidence has been
established to make the doctors think
twice before discarding the umbilical cords.