New Breakthrough In Nuclear Transfer
By Frank Yates, PhD, Suzanne Kadereit, PhD, Shannon McKinney-Freeman, PhD, Jason West, Heather Rooke, PhD.
In a new study published in the journal Science by Dr. Woo Suk Hwang and colleagues in Seoul, South Korea, the derivation of 11 new human embryonic stem cell lines using somatic cell nuclear transfer is described.
Human embryonic stem cells (hESC) were first isolated in 1998, from excess embryoscreated for fertility purposes, in Dr. James Thomson’s laboratory at the University of Wisconsin in Madison. Because these remarkable cells are capable of developing into any cell type of the body, many laboratories throughout the world are actively studying how they can be developed into cells with therapeutic potential, such as pancreatic islet cells, cells of the blood system and cells of the brain. Previous work on mouse embryonic stem cells has already yielded the conditions that direct these cells to produce heart cells, neurons, muscle and blood cells. Also, embryonic stem cells are capable of unlimited growth in a petri dish and can therefore generate an ample and sufficient supply of material to treat any patient.
However, important technical hurdles must still be overcome before embryonic stem cells can be used as standard therapy for any disease. Any treatment involving the transplantation of cells requires either life-long immunosuppression by various drugs, or complete compatibility between the donor cells and the patient. Only cell transplantation between identical twins would carry no risk of immune rejection. This is true for organ transplantation, bone marrow transplantation, and would also be true for the transplantation of cells derived from embryonic stem cells.
Although human embryonic stem cells have so far only been isolated from left over embryos donated from fertility clinics, it is possible to isolate human embryonic stem cells that are compatible to a patient by using a technique known as somatic cell nuclear transfer (SCNT) or therapeutic cloning (1). Nuclear transfer involves replacing the DNA of a donated egg with DNA from a patient’s cell. The egg is then coaxed into thinking it has been fertilized and develops for a few days in a petri dish, until embryonic stem cells can be removed. Since the new human embryonic stem cell line created through this technique is derived from the patient’s own cell, all the cells are a perfect match to the patient and thus, complications associated with immune rejection of transplanted cells are avoided; it would be nearly the same as receiving a transplant from an identical twin.
In February 2004, Dr. Hwang from South Korea (2) stunned the world by demonstrating for the first time that the nuclear transfer procedure (already routinely performed in animals) was also possible with human eggs and DNA. However, his team needed over 240 eggs to obtain one single human embryonic stem cell line. This high number of required eggs shed doubt on whether this technique could ever be used clinically, since egg retrieval from donors is an involved and risky procedure yielding about 10-12 eggs per retrieval.
In this new study published May 19 in the journal Science, Dr. Hwang and colleagues now describe the derivation of 11 new human embryonic stem cells lines by nuclear transfer. The study reports several major technical improvements that increased the efficiency more than ten-fold for the derivation of the human embryonic stem cell lines through nuclear transfer. Moreover, every cell line was derived in the complete absence of mouse feeder cells (3), which is a prerequisite for future clinical applications.
Most significantly, each human embryonic stem cell line created used DNA from patients suffering from serious conditions that could potentially be treated by cellular therapy , including congenital hypogammaglobulinemia (a blood disorder characterized by recurrent infections), spinal cord injury or juvenile diabetes. The age of the patients contributing the donor cell ranged from 2 to 56 years old. The derivation of human embryonic stem cells genetically identical to these patients represents a giant leap towards creating an inexhaustible supply of cells that can be exploited therapeutically. Furthermore, these new cell lines can also be used in basic research to study and elucidate the underlying causes of these diseases.
Researchers from any country where restrictive legislation does not prevent such work can now begin to use these cells as valuable tools to cure disease.
The impact of this work cannot be overstated. Dr. Hwang and colleagues have demonstrated that the creation of custom-made, immunologically compatible human embryonic stem cells is possible and practical. It represents a major step forward towards the reality of using human embryonic stem cells in the clinic.
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Posted:
June 9, 2005
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