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Somatic Cell Nuclear Transfer (SCNT) or Therapeutic Cloning
By Richard Mollard

Richard Mollard, Ph.D., is an embryonic stem cell specialist at the
Institute of Reproduction and Development at the Monash University in
Australia.

The major problem facing widespread use of embryonic stem cells in cell
therapies and organ replacement is their anticipated rejection by the
patient's immune system, which will recognize them as foreign. One way
around this problem would be to produce "custom" embryonic cells, matching
the patient's immunologic profile.

The approach, known as "therapeutic cloning," would lead to the production
of cells and tissue matching one's self, that would not elicit rejection
when the cells are transplanted into the patient.

For therapeutic cloning, also called somatic cell nuclear transfer (SCNT),
the DNA from any one cell in the body of a patient (usually a skin or muscle
cell) could be removed and transferred through microscopic glass tube into
an unfertilized egg that previously had its own DNA removed, as shown below
(first image below).

In a culture dish, the egg is then coaxed into developing as if it had been
fertilized. The one egg cell divides rapidly and generates a ball of cells,
called the blastocyst, in only 5-6 days. The inner cell mass, a part of the
blastocyst (middle image below), is then removed and embryonic stem cells
grown out of it. These embryonic stem cells, containing the patient's DNA,
now match the patient's immunological profile and will not be rejected by
the patient's immune system. These embryonic stem cells can now be used to
generate cells and tissues for the patient.

While this procedure sounds straightforward and is being performed quite
successfully to a certain degree in animal models, there are still technical
hurdles that need to be addressed before widespread use in humans.

For example, it is not yet clear how successfully entire sophisticated
organs could be generated in culture from embryonic stem cells. Culture
conditions are not sufficiently developed to mimic perfectly the environment
that contributes substantially to regulation of cell fate during
organogenesis.

In the nearer future, therapies would probably be restricted to injection of
tissue-specific progenitors that have been generated from the "custom"
embryonic stem cells, which then will contribute to the repair of damaged
organs in the patient.

An alternative approach to finding compatible stem cells for a given patient
is to establish banks with embryonic stem cells from a wide array of donors,
as is done for blood banks.

However, this approach will have the same limitations as organ donor and
bone marrow registries, i.e. the problem of limited availability of
compatible donors. This problem particularly affects ethnic minorities who
are of rarer type and are severely underrepresented in the organ and bone
marrow registries.


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