Research updates
Stem cells & therapeutic cloning   page 6
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4. The potential benefits of stem cell work    Link to the Medical Research Council web site
The cell membrane
There are several ways in which it is hoped to get round this problem of transplant rejection.
  1. Tissue typing
  2. Drugs to prevent rejection
  3. Therapeutic cloning
Have a look at page 1 of Engineering Antibodies for more on blood typing.
a. Tissue typing

One way would be to use tissue typing. This practice has routinely been used for decades when finding a suitable donor for a blood transfusion. For example, blood group AB can only be given to someone who is also AB. This is because a person who is blood group AB has both A and B antigens on their red blood cells. If, for example, this sort of blood is given to someone who is blood group O, the recipient's plasma has both anti-A and anti-B antibodies in it. As a result, massive agglutination occurs and the transfusion fails.

Tissue typing for the transplantation of whole organs is more complicated than for blood transfusions, but the principles are the same. If whole organs are one day grown from stem cells – and this is a very long way off – it has been estimated that perhaps only 20 stem cell lines would be needed to provide transplants for 90% of the UK population.
b. Drugs to prevent rejection
A different approach to the problem of rejection is to use drugs that prevent the recipient from rejecting any transplant organ. Again, this approach has been around for many years and is widely used with conventional organ transplants.
Figure 7. Possible way in which therapeutic cloning might be used to produce cell types that would have little or no chance of being rejected.

c. Therapeutic cloning
A third and novel approach has been proposed and is generally referred to as therapeutic cloning, though the use of this term is regretted by many of the scientists working in the area. These would be the steps in therapeutic cloning:

Step1: the patient needing a transplant would have one of their diploid cells removed – this could simply be a cell from the base of a hair or any other suitable tissue.
At the same time, an egg cell would be prepared by having its haploid nucleus removed.

Step 2: The patient cell, or its nucleus, would then be fused with the 'empty' egg cell. The result would be a diploid cell rather like a zygote.

Step 3: This cell would then be stimulated to divide by mitosis in the same way as the cell that gave rise to Dolly the cloned sheep was. If all went to plan, after about five days a blastocyst would develop.

Step 4: Stem cells could then be isolated from the blastocyst and encouraged to develop into specific tissue types.

Step 5: These tissues could be used to transplant back into the patient.

How does therapeutic cloning differ from embryonic growth?
The crucial difference between this procedure and the one illustrated in Figure 5 is that the therapeutic cloning illustrated in Figure 6 results in cell lines, and perhaps eventually organs for transplantation, that are genetically almost identical with the patient from whom the original diploid cell was taken.
Figure 8. The developmental fate of mice embryonic stem cells depends on the level of the protein Oct-3/4. Mesoderm develops into various internal organs; endoderm into the lining of the gut and trophectoderm into the placenta.

When will this happen?
It must be emphasised that the hoped-for benefits of stem cell research indicated in Figures 6 and 7 are many years ahead. One problem is that we still have very little idea about what causes stem cells to develop into particular cell types. Some initial work in this area suggests that the levels of certain proteins may be critical. In mice, for example, a protein called Oct-3/4 seems to be involved. Joint research between Austin Smith of the University of Edinburgh and Hotishi Niwa of Osaka University in Japan has shown that altering the level of Oct-3/4 seems to determine the cell type into which stem cells obtained from mice embryos develop (Figure 8).
Question 5
a) Why do you think many of the scientists working in the field of stem cell research regret the use of the term 'therapeutic cloning'?
b) Why would the cell types shown in Figure 7 not be exactly the same genetically as the patient's cells?
c) How would therapeutic cloning differ from the reproductive cloning used to produce Dolly the sheep?
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