An international team of scientists led by Dr. Shoukhrat Mitalipov at the Oregon Health & Science University, USA, succeeded for the first time ever in cloning human embryonic stem cells by somatic cell nuclear transfer. This breakthrough raises questions about the potentials and dangers of creating human stem cells by cloning. Prof. Dr. Marcel Leist from the University of Konstanz, who uses human embryonic stem cells for his research, gives an assessment of this accomplishment in an interview with Bettina Baumann on behalf of BIOPRO.
The landmark discovery is mainly of a technical nature. Cloning is a technique that is thousands of years old and relates to the creation of genetically identical individuals which may also occur in nature as a result of asexual reproduction. Therefore, I personally would not use the verb to clone.
The authors use one of several cloning techniques, namely the transfer of a nucleus from a somatic cell into an egg cell. This method, which is known as somatic-cell nuclear transfer (SNCT), was developed by John Gurdon 50 years ago and awarded the Nobel Prize in Physiology and Medicine in 2012. SCNT was used to create the famous sheep Dolly and thousands of other animals. The same technique has now been applied to human cells. The main thing the researchers had to do was to adapt the culture media in which the cells are growing to human cells.
An embryo normally develops from fertilised egg cells and has the same genetic properties as the fertilised egg. If you want other genetic characteristics, you have to provide other genetic information. This information is stored in the cell nucleus. In practice, the nucleus is therefore removed from the egg cell and replaced with the nucleus of another cell, e.g. of a skin cell of the person to be cloned. Then the egg is left to develop normally, in animals using surrogate mothers, for example.
This is to a large extent certainly due to the fact that this type of research is not possible in many countries. You need human egg cells whose availability is limited and regulated by law. Therefore, such work was carried out with bovine egg cells and human cell nuclei in England a few years ago. Since there is no practical application, only a handful of laboratories have actually been working on human SCNT.
The publication by the team of researchers led by Shoukhrat Mitalipov suggests that both are very similar. Whether the technique is suitable for producing a human being is not known, as it is forbidden. However, it is known from animal experiments that creating clones with SCNT is more difficult than it would seem. SCNT can lead to minor damage, and the reprogramming of the body cell might also be incomplete. And this is usually not noticed in the early stages of development. A lot of work is still needed to further optimise the method.
iPS are legal and also ethically less problematic. The technique does not involve eggs, destruction of embryos and physical manipulation of the cell nuclei. The iPS method reprogrammes adult cells to an embryonic state to produce iPS. Simply put, a skin cell is directly transformed into a cell that corresponds to a fertilised egg cell by the addition of ‘chemicals’. This can be done for both women and men. Such iPS cells can then be turned into any type of cell, nerve or liver cells, which can be transplanted with no problem into the patient whose cells have been used for the production of iPS cells.
The iPS technology is at a developed and established stage. So I do not think that the SCNT technology, which is far more difficult and more problematic, could be an alternative. Particularly in Germany, I do not foresee any developments in this direction as we do not work with SCNT here. Perhaps there are niche applications for the regenerative treatment of diseases caused by mitochondrial mutations. Strictly speaking, only slightly more than 99.9% of the genetic information is in fact stored in the nucleus, the rest is stored in the mitochondria. In iPS cells, these cell organelles originate from the mitochondria of the cell donor. Any existing damage in the mitochondrial genome is therefore still present after the conversion of the donated cells into iPS cells. The SCNT technique therefore offers an easy way to provide healthy mitochondria since only the nucleus is derived from the patient and the mitochondria are taken directly from the donor egg cell.
Certainly not in Western democracies. The iPS technology is also an alternative for many applications and is firmly established. There is no problem with it. However, last year’s Nobel Prize and the work of John Gurdon and Shinya Yamanaka related to the reprogramming of somatic cells into pluripotent stem cells have, like all other big discoveries, changed our understanding of the world. And society has to deal with such discoveries. Our world has changed since we know that we can reproduce by way of a skin cell or a drop of blood, or at least grow replacement organs. In Austria, there is a company that produces urine-derived iPS, enabling cells to be obtained from any consenting individual without surgical intervention.
Professor Dr. Marcel Leist is the head of the Doerenkamp-Zbinden Chair of in-vitro Technology and Biomedicine at the University of Konstanz. He explores pharmacological and toxicological mechanisms, methods and model systems related to the development of and damage to the nervous system. He uses embryonic stem cells to generate otherwise inaccessible cell types which can be used to investigate neurodegenerative diseases or neurotoxic substances. In addition, his laboratory uses stem cells for the investigation of the effects of harmful substances during neuronal development.
Original publication:Human Embryonic Stem Cells Derived by Somatic Cell Nuclear TransferMasahito Tachibana, Paula Amato, Michelle Sparman, Nuria Marti Gutierrez, Rebecca Tippner-Hedges, Hong Ma, Eunju Kang, Alimujiang Fulati, Hyo-Sang Lee, Hathaitip Sritanaudomchai, Keith Masterson, Janine Larson, Deborah Eaton, Karen Sadler-Fredd, David Battaglia, David Lee, Diana Wu, Jeffrey Jensen, Phillip Patton, Sumita Gokhale, Richard L. Stouffer, Don Wolf, Shoukhrat Mitalipov; Cell - 6 June 2013 (Vol. 153, Issue 6, pp. 1228-1238)
Further information:Prof. Dr. Marcel LeistFaculty of BiologyUniversiy of Konstanz E-mail: marcel.leist(at)uni-konstanz.de