‘Human-Cloning’ to Make Personalized Embryonic Stem Cells

Personalized embryonic stem cells have been created for the first time using genetic material taken from adult skin cells and transferred into a human egg. The researchers, working at the New York Stem Cell Foundation Laboratory, managed to grow the resulting cell to produce an early stage embryo, thus giving scientists the possibility of creating a reservoir of embryonic stem cells perfectly matched to an individual patient.

Stem Cell Cloning and Dolly the Sheep

The researchers, led by Dr Dieter Egli, have expressed caution over the technique as there remained significant questions over its safety and reliability in human cloning. The stem cells created still contained both the adult and the egg cells’ chromosomes and the technique of somatic cell nuclear transfer will be familiar to those who remember Dolly the sheep, the first cloned mammal who was brought to public attention in 1997. The researchers thought that they had found a way around the problem of the embryo containing both sets of chromosomes by replacing the egg cell’s genetic material with the chromosomes of a skin cell. However, although the egg divided, it failed to progress past the 6-12 cell stage.

Growing a Cloned Embryo

Instead, the researchers left the egg’s own chromosomes in place and then added the skin chromosomes. This led to the the egg developing to the blastocyst stage, which is the usual source of embryonic stem cells. However, the two adult copies in the skin cell and the single copy in the egg cell meant that three sets of chromosomes, rather than the usual two were present in the resulting cell, which can cause problems. Conditions such as Down’s Syndrome are caused by having three copies of just one chromosome, and some embryos without the correct number of chromosomes do not develop at all.

Cloned Embryonic Stem Cell Research

Developing a technique to create embryonic stem cells containing a patient’s own genetic material is extremely exciting. Embryonic stem cell treatments currently under investigation, such as the one for Stargardt’s Macular Dystrophy in the UK do not use the patient’s own cells and so require immunosuppressant drugs to prevent immune system rejection of the transplant material. Scientists will need to create embryonic stem cells containing just the donor DNA as the cell division that takes place means that the chromosomes are combined in the resulting cells’ nuclei, making separation of the genetic material extremely complex, if not impossible.

Stem Cell Treatments for Chronic Illness

The increased efficiency of the technique developed by Egli and his team gives fellow researchers an insight into the problems of producing embryonic stem cells. In this particular study, the patients who donated skin cells were type 1 diabetics and the hope is that, in the future, such patients would be helped by stem cell treatments to regenerate or replace the insulin-producing cells damaged by the condition. The nuclei of the patients’ cells were extracted and transplanted to unfertilized donor oocytes (egg cells). The researchers then demonstrated that leaving the oocyte’s nucleus intact and adding the skin cell nucleus to the egg cell led to the adult nucleus being reprogrammed back to a pluripotent stage. Pluripotency means that the cell can, theoretically, go on to become any type of cell in the body as it is these pluripotent embryonic stem cells that grow to produce a human being. The cloned embryonic stem cells could then be used to produce pancreatic beta-cells for diabetics, nerve cells for patients with motor neuron disease, liver cells for those with cirrhosis, and any other cell type needed to repair and restore the body.

Creating a Stem Cell Bank

The presence of three sets of chromosomes in the cloned embryonic stem cells means that the cells cannot yet be used for therapeutic purposes, but the researchers are hopeful of understanding the role of the oocyte chromosome in the near future, so as to create patient-specific stem cell cells suitable for stem cell treatments. Theoretically, such a technique could also create stem cell banks available to help patients when the need arises in much the same way as a patient would be added to an organ donor waiting list. Complete reprogramming of an adult cell nucleus by insertion into an unfertilized oocyte is an exciting step towards therapeutic cloning of stem cells for therapeutic use in a variety of conditions and also gives researchers a way out of the ethical dilemma of using existing embryos for stem cell research.

Reference

Scott Noggle, Ho-Lim Fung, Athurva Gore, Hector Martinez, Kathleen Crumm Satriani, Robert Prosser, Kiboong Oum, Daniel Paull, Sarah Druckenmiller, Matthew Freeby, Ellen Greenberg, Kun Zhang, Robin Goland, Mark V. Sauer, Rudolph L. Leibel, Dieter Egli. Human oocytes reprogram somatic cells to a pluripotent state. Nature, 2011; 478 (7367)