The First Report of Successful Human Nuclear Transfer for Stem Cells
By Richard Mollard

On March 12, 2004, in the peer reviewed journal Science(1), Woo Suk Hwang and his colleagues from Korea reported the creation of a human blastocyst by somatic cell nuclear transfer and the subsequent derivation of human embryonic stem cells. This report was a ground-breaking step forward in stem cell research and its ramifications are outlined below.

Nuclear transfer is the technique used to generate personalized stem cells and generally refers to the transfer of a cell nucleus (i.e. the DNA) from a mature cell into an unfertilized egg, or oocyte, from which the nucleus had been previously removed mechanically or destroyed. The manipulated egg is then coaxed into dividing as if it had been fertilized, and starts to develop in the culture dish.

For reproductive cloning, the developing egg is then transferred into a surrogate mother for pregnancy and the delivery of living offspring. Although reproductive cloning using human tissues is considered an unacceptable procedure by the scientific community and public throughout the world, reproductive cloning has been used to create cloned progeny of a diverse range of animal species, including sheep (e.g. Dolly), rhesus monkeys, mice, cows, goats and pigs(2).

It is important, however, to note that extremely few live births have been achieved in animals compared to the large numbers of eggs that were manipulated and transferred. Moreover, the few live born animals have had major health defects, demonstrating that reproductive cloning is not safe.

Nuclear transfer for stem cells, on the other hand, represents a more restricted process than reproductive cloning, because the manipulated egg is not transferred for pregnancy, but rather is permitted to develop in culture to the blastocyst stage such that embryonic stem cells can be produced. Embryonic stem cells are believed to hold tremendous potential for the production of cells or tissues for treating many disorders, for example, blood disorders, diabetes and Parkinson's disease. However, if the embryonic stem cells that are to be used for therapy do not contain the patient's own DNA, they would most likely be rejected by the patient's immune system. Thus, nuclear transfer for stem cells could potentially provide genetically compatible stem cells, by introducing one's own DNA into donor eggs and deriving cells and tissues for transplantation that express one's own genes. This process circumvents issues of rejection by one's immune system. The ground-breaking report by the Korean team demonstrated that this technique was possible with human eggs and DNA, thus opening the door to human therapy.

In other exciting experiments using mice, nuclear transfer has been combined with gene therapy, to repair a genetic mutation which confers a blood disorder(3). This particular blood disorder resulted in severe immunodeficiency caused by the loss of immunoglobulins and mature immune cells within the blood. In these experiments, the researchers produced mouse embryonic stem cells by nuclear transfer using DNA taken from the tip of the tail of one of the immunodeficient mice. The genetic mutation in the derived embryonic stem cells was then repaired by gene therapy. The repaired embryonic stem cells were grown into blood progenitor cells in culture and transplanted into the immunodeficient mice. These experiments succeeded in partially curing the mice.

Now that the Korean team has demonstrated that nuclear transfer of human DNA into human eggs is possible, the same approach could be applied to developing therapies to correct genetic diseases in humans. However, the technique involving human eggs and DNA is a controversial issue because of the requirement to destroy the blastocyst, or early human conceptus, in order to produce the embryonic stem cells. The legality of undertaking nuclear transfer for generating stem cells using human tissue is thus governed on a country by country basis and is presently legal in countries such as Belgium, China, South Korea, Singapore and the United Kingdom(4). If the expectation to produce every functional cell type of the body with human embryonic stem cells is realized in the future, nuclear transfer technique holds the real potential for providing personalized tissues for the repair of organs, avoiding the risk of immune rejection. For this reason, the report by Hwang et al. is significant, as they showed, for the first time, that nuclear transfer with human material was technically possible.

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

1 Hwang et al., 2004, Science, 303, p1669
2 Mollard et al., 2002, Differentiation, 70, p109
3 Rideout et al., 2002, Cell, 109, p17
4 Knowles, 2004, Nature Biotech., 22, p157

Updated: February 2, 2005