Cloning method used to make stem cells

Behind the Headlines

Thursday October 6 2011

As embryos develop stem cells become specialised

A form of cloning has been used to create embryonic stem cells in humans, The Daily Telegraph reported today. The newspaper said that for the first time scientists have grown tailor-made embryonic stem cells using human egg cells.

In recent years, stem cells have become a key study area for researchers as they have the unique ability to turn into a range of other specialised cells, and therefore could be used to replace cells lost or damaged by disease and injury.

The news is based on research that looked at experimental techniques to develop embryonic stem cells that carry a selected individual’s DNA, and therefore might avoid problems such as rejection by the immune system.

The researchers used a method that takes the genetic material from a mature cell and transfers it into a donated egg cell. They found that the technique only worked if the egg’s genetic material was left intact. However, this created a group of cells that contained three copies of each chromosome, instead of the two found in normal human cells.

This research is a step in the challenging attempt to develop ‘personalised’ human stem cells for the treatment of disease. However, it is important to remember that these cells are not genetically normal, and further research will be needed to work out a way to make the cells only carry the correct number of chromosomes.

The study is likely to raise ethical issues that will also require continued discussion. All of these issues will need to be scrutinised before the technique could be used for therapeutic purposes.

 

Where did the story come from?

The study was carried out by researchers from the New York Stem Cell Foundation, the University of California at San Diego, and Columbia University in the US. The research was funded by the University of California at San Diego, the New York Stem Cell Foundation and the Russell Berrie Foundation, also in the US.

The study was published in the peer-reviewed scientific journal Nature.

The media reported the research accurately, generally highlighting both the small-step nature of the results as well as some of the ethical considerations. The Independent’s headline that the research may lead to a cure for Parkinson’s disease or diabetes is, however, premature. The same article reported that the egg cells were ‘spare cells’ from IVF treatment, which is incorrect; the eggs were donated specifically for research.

 

What kind of research was this?

This was a series of laboratory experiments aiming to discover whether a cloning technique called ‘somatic cell nuclear transfer’ (SCNT) could be used to generate human embryonic stem cells containing the genetic material from a selected adult cell.

SCNT has previously been used to transfer genetic material from adult cells into an unfertilised egg cell. The researchers hypothesised that the technique could be extended so that it would generate stem cells that carry a patient’s unique genetic information. The ability to generate ‘personalised’ cells could potentially allow doctors to repair or replace patients’ cells damaged or destroyed by illness, while avoiding the risk of rejection that would come with receiving tissue from another person.

In normal human development the egg is fertilised and then continuously divides to form an embryo, with stem cells developing into tissue and organs. The researchers wanted to develop a method to harness this process by introducing a full set of a person’s chromosomes into an unfertilised egg and making it generate personalised stem cells that could develop into a wide variety of tissues.

This type of experimental laboratory research is essential for developing the techniques that would be needed to produce this type of cell, although there would still need to be a great deal of further development before it could be considered for clinical testing. Alongside technical evaluations of the process, it is also likely that the ethical implications of this technology would need to be examined thoroughly.

 

What did the research involve?

The researchers used human egg cells that had been donated by women participating in an egg donation programme. Such programmes are common in the US for reproductive purposes, with the eggs being used for fertility treatments. In this case, the women were given the option to donate their eggs for either reproductive or research purposes. The women were paid for their eggs, regardless of which option they chose.

The initial set of experiments involved removing the egg’s genetic material (a single set of chromosomes), isolating the genetic material (a paired set of chromosomes) from a type of mature cell called a fibroblast, and transferring the fibroblast’s genetic material into the egg cell. Some of the experiments used fibroblasts obtained from the skin cells of an adult male with diabetes, and others from a healthy adult male. The researchers then monitored the cells to determine whether or not they were dividing and producing clusters of cells as expected.

The second set of experiments involved leaving the egg’s genetic material intact, and adding the genetic material from the fibroblasts. The researchers again monitored the cells to determine whether or not they were developing as expected.

If the cells divided and developed to the blastocyst stage, which is the stage at which stem cells begin to develop, the researchers then removed the stem cells from this collection of cells, and examined the resulting genetic material they contained. Next, they determined whether or not the cells acted like embryonic stem cells, and whether they were capable of developing into a group of cells called germ layers, as would be seen in the development of a normal embryo. Different germ layers will then develop into different tissues and organs in the body during normal embryonic development.

 

What were the basic results?

The researchers found that when they removed the egg cell’s genetic material (a single set of chromosomes) before transferring in the genetic material from the fibroblast (a paired set of chromosomes), the egg cell did not divide enough to reach the stage where stem cells develop.

When the egg cell’s genetic material was left in the cell, and the fibroblast’s genetic material was added, the cell divided to the point where stem cells developed. These stem cells contained three sets of chromosomes instead of the usual two. Despite the extra chromosome, the cells were found to be capable of differentiating (or developing) into the germ layers that eventually go on to form human tissue and organs.

 

How did the researchers interpret the results?

The researchers concluded that removing the egg cell’s genetic material before transferring in the target genetic material was not a viable option for generating stem cells for therapeutic purposes. They thought this might be because the egg’s nucleus, which contains its genetic material, may also contain molecules that are required for embryonic cells to divide and develop appropriately.

The researchers say that generating embryonic stem cells that carry the patient’s unique genetic information could be used to replace their cells in the treatment of degenerative diseases.

 

Conclusion

This research is an exciting step in the development of stem cell research, and the possibility of using the cells for the treatment of disease. However, research is still at an early, developmental stage, and is a long way off from being used as a therapy.

Experts say this is the first instance of researchers transferring the genetic material of an adult human cell into an egg cell in order to generate human stem cells capable of differentiating into any other type of cell.

They also say the research exposes unanticipated technical difficulties in using this technique, as the process only worked when the genetic material of the donated egg cell was left inside the newly-formed cell. Leaving the egg’s own genetic material intact meant that the resulting cell had three copies of each chromosome (rather than the usual two) and genetic material from both the donor egg and the donor adult cell. As such it is unknown whether this cell would behave in the same way that a normal cell with two sets of chromosomes would.

Also, the cell would not strictly be considered a cloned cell as its genetic material did not exactly match that found in the original fibroblast cell.

Additional research is needed before this method could offer a viable method of generating therapeutic stem cells. It would not be possible to use the cells generated in this research in a therapeutic setting due to their genetic abnormalities.

Stem cell research is also the subject of much ethical debate, especially surrounding the extraction of the cells from human embryos. This technique offers an alternative to such methods as it uses unfertilised egg cells, but it does raise ethical considerations of its own.

When discussing their work the study’s authors say their research demonstrated that it is possible to transfer genetic material from a mature human cell into an unfertilised egg and induce the egg into dividing and producing embryonic stem cells. They say that further research is needed to determine how to use this technique to develop stem cells with the correct number of chromosomes. This step would appear to be the vital difference between creating cells that would be unsuitable for human use and those that might have therapeutic potential.

The researchers also say that in order to further develop this technique, a reliable supply of human egg cells is needed. It is likely that this requirement will spur much ethical debate, especially surrounding the ethics of paying women for donating their eggs and using cloning techniques.

Overall, this work does seem to provide an advance towards devising a new technique for creating personalised stem cells. However, the process of developing promising experimental techniques into clinically viable ones is long, complicated and unpredictable, and there are still a number of technical and ethical issues that must be addressed before the technology can be directly used to treat patients.

Links to the headlines

Stem cell breakthrough may lead to cure for Parkinson's and diabetes. The Independent, October 6 2011

'Cloning' used to create embryonic stem cells in humans. The Daily Telegraph, October 6 2011

Human 'cloning' makes stem cells. BBC News, October 6 2011

New technique to clone stem cells. Financial Times, October 6 2011

Stem cell 'cloning' techniques hailed as new breakthrough in medicine. Metro, October 6 2011

Links to the science

Noggle S, Fung HL, Gore A et al. Human oocytes reprogram somatic cells to a pluripotent state. Nature, Volume: 478, Pages: 70-75

Further reading

Related editorials

Daley GQ and Solbakk JH. Stem cells: Triple genomes go far. Nature, Volume: 478, Pages: 40-41

Hyun I and Tesar P. Stem cells: Cloning advance calls for careful regulation. Nature, Volume: 478, Pages: 36-37

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Analysis by Bazian

Edited by NHS Choices