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Somatic cell nuclear transfer

Somatic cell nuclear transfer

Overview
In genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....

 and developmental biology
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...

, somatic-cell nuclear transfer (SCNT) is a laboratory technique for creating a clonal embryo, using an ovum
Ovum
An ovum is a haploid female reproductive cell or gamete. Both animals and embryophytes have ova. The term ovule is used for the young ovum of an animal, as well as the plant structure that carries the female gametophyte and egg cell and develops into a seed after fertilization...

 with a donor nucleus (see process below). It can be used in embryonic stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...

 research, or, potentially, in regenerative medicine
Regenerative medicine
Regenerative medicine is the "process of replacing or regenerating human cells, tissues or organs to restore orestablish normal function". This field holds the promise of regenerating damaged tissues and organs in the body by replacing damaged tissue and/or by stimulating the body's own repair...

 where it is sometimes referred to as "therapeutic cloning". It can also be used as the first step in the process of reproductive cloning
Cloning
Cloning in biology is the process of producing similar populations of genetically identical individuals that occurs in nature when organisms such as bacteria, insects or plants reproduce asexually. Cloning in biotechnology refers to processes used to create copies of DNA fragments , cells , or...

.

In SCNT, the nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

 is removed and the rest of the cell discarded.
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Encyclopedia
In genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....

 and developmental biology
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...

, somatic-cell nuclear transfer (SCNT) is a laboratory technique for creating a clonal embryo, using an ovum
Ovum
An ovum is a haploid female reproductive cell or gamete. Both animals and embryophytes have ova. The term ovule is used for the young ovum of an animal, as well as the plant structure that carries the female gametophyte and egg cell and develops into a seed after fertilization...

 with a donor nucleus (see process below). It can be used in embryonic stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...

 research, or, potentially, in regenerative medicine
Regenerative medicine
Regenerative medicine is the "process of replacing or regenerating human cells, tissues or organs to restore orestablish normal function". This field holds the promise of regenerating damaged tissues and organs in the body by replacing damaged tissue and/or by stimulating the body's own repair...

 where it is sometimes referred to as "therapeutic cloning". It can also be used as the first step in the process of reproductive cloning
Cloning
Cloning in biology is the process of producing similar populations of genetically identical individuals that occurs in nature when organisms such as bacteria, insects or plants reproduce asexually. Cloning in biotechnology refers to processes used to create copies of DNA fragments , cells , or...

.

The process


In SCNT, the nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

 is removed and the rest of the cell discarded. At the same time, the nucleus of an egg cell is removed. The reason for this is to discard the unwanted host's DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

. The nucleus of the somatic cell is then inserted into the enucleated egg cell. Alternatively, the entire donor cell may be fused with the enucleated egg cell. After being inserted into the egg, the somatic-cell nucleus is reprogrammed
Reprogramming
Reprogramming refers to erasure and remodeling of epigenetic marks, such as DNA methylation, during mammalian development. After fertilization some cells of the newly formed embryo migrate to the germinal ridge and will eventually become the germ cells...

 by the host cell. The egg, now containing the nucleus of a somatic cell, is stimulated with a shock and will begin to divide. After many mitotic divisions in culture, this single cell forms a blastocyst
Blastocyst
The blastocyst is a structure formed in the early embryogenesis of mammals, after the formation of the morula. It is a specifically mammalian example of a blastula. It possesses an inner cell mass , or embryoblast, which subsequently forms the embryo, and an outer layer of cells, or trophoblast,...

 (an early stage embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...

 with about 100 cells) with almost identical DNA to the original organism.
The technique of transferring a nucleus from a somatic cell into an egg that produced Dolly was an extension of experiments that had been ongoing for over 40 years. In the simplest terms, the technique used to produce Dolly the sheep – somatic-cell nuclear transplantation cloning – involves removing the nucleus of an egg and replacing it with the diploid nucleus of a somatic cell.

SCNT in stem cell research


Some researchers use SCNT in stem cell research. The aim of carrying out this procedure is to obtain stem cells that are genetically
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....

 matched to the donor organism. Presently, no human stem cell lines have been derived from SCNT research.

Embryonic stem cells are new, unspecialized cells that are able to be produced into a specialized cell that can replace another cell that has been lost in the body.


A potential use of genetically-customized stem cells would be to create cell lines that have genes linked to the particular disease. For example, if a person with Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

 donated his or her somatic cells, then the stem cells resulting from SCNT would have genes that contribute to Parkinson's disease. In this scenario, the disease specific stem cell lines would be studied in order to better understand the disease.

In another scenario, genetically-customized stem cell lines would be generated for cell-based therapies to transplant to the patient. The resulting cells would be genetically identical to the somatic-cell donor, thus avoiding any complications from immune system rejection
Transplant rejection
Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after...

.

Only a handful of the labs in the world are currently using SCNT techniques in human stem cell research. In the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

, scientists at the Harvard Stem Cell Institute, the University of California San Francisco
University of California, San Francisco
The University of California, San Francisco is one of the world's leading centers of health sciences research, patient care, and education. UCSF's medical, pharmacy, dentistry, nursing, and graduate schools are among the top health science professional schools in the world...

, Stemagen (La Jolla, CA) and possibly Advanced Cell Technology
Advanced Cell Technology
Advanced Cell Technology, Incorporated , is a biotechnology company located in Marlborough, Massachusetts, USA. The company specializes in the development and commercialization of cell therapies for the treatment of a variety of diseases...

 are currently researching a technique to use somatic-cell nuclear transfer to produce embryonic stem cell
Embryonic stem cell
Embryonic stem cells are pluripotent stem cells derived from the inner cell mass of the blastocyst, an early-stage embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells...

s. In the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...

, the Human Fertilisation and Embryology Authority
Human Fertilisation and Embryology Authority
The Human Fertilisation and Embryology Authority is a statutory body in the United Kingdom that regulates and inspects all UK clinics providing in vitro fertilisation, artificial insemination and the storage of human eggs, sperm or embryos. It also regulates Human Embryo research...

 has granted permission to research groups at the Roslin Institute and the Newcastle Centre for Life
Centre for Life
The Centre for Life is a science centre located in the city centre of Newcastle upon Tyne, England. It is an educational charity which aims to promote greater interest and engagement in science as well as supporting scientific research...

. SCNT may also be occurring in China.

In 2005, a South Korea
South Korea
The Republic of Korea , , is a sovereign state in East Asia, located on the southern portion of the Korean Peninsula. It is neighbored by the People's Republic of China to the west, Japan to the east, North Korea to the north, and the East China Sea and Republic of China to the south...

n research team led by Professor Hwang Woo-suk
Hwang Woo-Suk
Hwang Woo-suk is a South Korean veterinarian and researcher. He was a professor of theriogenology and biotechnology at Seoul National University who became infamous for fabricating a series of experiments, which appeared in high-profile journals, in the field of stem cell research...

, published claims to have derived stem cell lines via SCNT, but supported those claims with fabricated data. Recent evidence has proved that he in fact created a stem cell line from a parthenote
Parthenogenesis
Parthenogenesis is a form of asexual reproduction found in females, where growth and development of embryos occur without fertilization by a male...

.

The impetus for SCNT-based stem cell research has been decreased by the development and improvement of alternative methods of generating stem cells. Methods to reprogram normal body cells into pluripotent stem cells
Induced pluripotent stem cell
Induced pluripotent stem cells, commonly abbreviated as iPS cells or iPSCs are a type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing a "forced" expression of specific genes....

 were developed in humans in 2007. The following year, this method achieved a key goal of SCNT-based stem cell research: the derivation of pluripotent stem cell lines that have all genes linked to various diseases. Some scientists working on SCNT-based stem cell research have recently moved to the new methods of induced pluripotent stem cells.

SCNT in reproductive cloning


This technique is currently the basis for cloning
Cloning
Cloning in biology is the process of producing similar populations of genetically identical individuals that occurs in nature when organisms such as bacteria, insects or plants reproduce asexually. Cloning in biotechnology refers to processes used to create copies of DNA fragments , cells , or...

 animals (such as the famous Dolly the sheep
Dolly the Sheep
Dolly was a female domestic sheep, and the first mammal to be cloned from an adult somatic cell, using the process of nuclear transfer. She was cloned by Ian Wilmut, Keith Campbell and colleagues at the Roslin Institute near Edinburgh in Scotland...

), and in theory could be used to clone humans. However, most researchers believe that in the foreseeable future it will not be possible to use this technique to produce a human clone that will develop to term. However, it is still a possibility and can become more probable in the future as it will probably need a few more adjustments to work for humans.

Limitations


Stresses placed on both the egg cell and the introduced nucleus are enormous, leading to a high loss in resulting cells. For example, Dolly the sheep was born after 277 eggs were used for SCNT, which created 29 viable embryos. Only three of these embryos survived until birth, and only one survived to adulthood. As the procedure currently cannot be automated, but has to be performed manually under a microscope
Microscope
A microscope is an instrument used to see objects that are too small for the naked eye. The science of investigating small objects using such an instrument is called microscopy...

, SCNT is very resource intensive. The biochemistry
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...

 involved in reprogramming the differentiated
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...

 somatic cell nucleus and activating the recipient egg is also far from understood.

In SCNT, not all of the donor cell's genetic information is transferred, as the donor cell's mitochondria that contain their own mitochondrial DNA
Mitochondrial DNA
Mitochondrial DNA is the DNA located in organelles called mitochondria, structures within eukaryotic cells that convert the chemical energy from food into a form that cells can use, adenosine triphosphate...

 are left behind. The resulting hybrid cells retain those mitochondrial structures which originally belonged to the egg. As a consequence, clones such as Dolly that are born from SCNT are not perfect copies of the donor of the nucleus.

Controversy



Proposals to use nucleus transfer techniques in human stem cell research raise a set of concerns beyond the moral status of any created embryo. These have led to some individuals and organizations who are not opposed to human embryonic stem cell research to be concerned about, or opposed to, SCNT research.

One concern is that blastula creation in SCNT-based human stem cell research will lead to the reproductive cloning of humans. Both processes use the same first step: the creation of a nuclear transferred embryo, most likely via SCNT. Those who hold this concern often advocate for strong regulation of SCNT to preclude implantation of any derived products for the intention of human reproduction, or its prohibition.

A second important concern is the appropriate source of the eggs that are needed. SCNT requires human eggs
Ovum
An ovum is a haploid female reproductive cell or gamete. Both animals and embryophytes have ova. The term ovule is used for the young ovum of an animal, as well as the plant structure that carries the female gametophyte and egg cell and develops into a seed after fertilization...

, which can only be obtained from women. The most common source of these eggs today are eggs that are produced and in excess of the clinical need during IVF treatment. This is a minimally invasive procedure, but it does carry some health risks, such as ovarian hyperstimulation syndrome
Ovarian hyperstimulation syndrome
Ovarian hyperstimulation syndrome is a complication from some forms of fertility medication. Most cases are mild, but a small proportion are severe.-Causative medications:...

, and in very rare instances even death.

One vision for successful stem cell therapies is to create custom stem cell lines for patients. Each custom stem cell line would consist of a collection of identical stem cells each carrying the patient's own DNA, thus reducing or eliminating any problems with rejection when the stem cells were transplanted for treatment. For example, to treat a man with Parkinson's disease, a cell nucleus from one of his cells would be transplanted by SCNT into an egg cell from an egg donor, creating a unique lineage of stem cells almost identical to the patient's own cells. (There would be differences. For example, the mitochondrial DNA would be the same as that of the egg donor. In comparison, his own cells would carry the mitochondrial DNA of his mother.)

Potentially millions of patients could benefit from stem cell therapy, and each patient would require a large number of donated eggs in order to successfully create a single custom therapeutic stem cell line. Such large numbers of donated eggs would exceed the number of eggs currently left over and available from couples trying to have children through assisted reproductive technology
Assisted reproductive technology
Assisted reproductive technology is a general term referring to methods used to achieve pregnancy by artificial or partially artificial means. It is reproductive technology used primarily in infertility treatments. Some forms of ART are also used in fertile couples for genetic reasons...

. Therefore, healthy young women would need to be induced to sell eggs to be used in the creation of custom stem cell lines that could then be purchased by the medical industry and sold to patients. It is so far unclear where all these eggs would come from. The sale of human eggs is normally referred to as a "donation", but women who donate their eggs are often paid thousands of dollars.

Stem cell experts consider it unlikely that such large numbers of human egg donations would occur in developed country because of the unknown long-term public health effects of treating large numbers of healthy young women with heavy doses of hormones in order to induce hyperovulation (ovulating several eggs at once). Although such treatments have been performed for several decades now, the long-term effects have not been studied or declared safe to use on a large scale on otherwise healthy women. Longer-term treatments with much lower doses of hormones are known to increase the rate of cancer decades later. Whether hormone treatments to induce hyperovulation could have similar effects is unknown. There are also ethical questions surrounding paying for eggs. In general, marketing body parts is considered unethical and is banned in most countries. Human eggs have been a notable exception to this rule for some time.

To address the problem of creating a human egg market, some stem cell researchers are investigating the possibility of creating artificial eggs. If successful, human egg donations would not be needed to create custom stem cell lines. However, this technology may be a long way off.

Policies regarding human SCNT


SCNT involving human cells is currently legal for research purposes in the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...

, having been incorporated into the Human Fertilisation and Embryology Act 1990
Human Fertilisation and Embryology Act 1990
The 1990 Human Fertilisation and Embryology Act is an Act of the Parliament of the United Kingdom.-Coverage:The act covers several areas:# The licensing of human fertility treatment involving the use of donated genetic material ....

 in 2001. Permission must be obtained from the Human Fertilisation and Embryology Authority
Human Fertilisation and Embryology Authority
The Human Fertilisation and Embryology Authority is a statutory body in the United Kingdom that regulates and inspects all UK clinics providing in vitro fertilisation, artificial insemination and the storage of human eggs, sperm or embryos. It also regulates Human Embryo research...

 in order to perform or attempt SCNT.

In the United States, the practice remains legal, as it has not been addressed by federal law. However, in 2002, a moratorium on United States federal funding for SCNT prohibits funding the practice for the purposes of research. Thus, though legal, SCNT cannot be federally funded.
In 2003, the United Nations
United Nations
The United Nations is an international organization whose stated aims are facilitating cooperation in international law, international security, economic development, social progress, human rights, and achievement of world peace...

 adopted a proposal submitted by Costa Rica
Costa Rica
Costa Rica , officially the Republic of Costa Rica is a multilingual, multiethnic and multicultural country in Central America, bordered by Nicaragua to the north, Panama to the southeast, the Pacific Ocean to the west and the Caribbean Sea to the east....

, calling on member states to "prohibit all forms of human cloning in as much as they are incompatible with human dignity and the protection of human life." This phrase may include SCNT, depending on interpretation.

The Council of Europe's
Council of Europe
The Council of Europe is an international organisation promoting co-operation between all countries of Europe in the areas of legal standards, human rights, democratic development, the rule of law and cultural co-operation...

 Convention on Human Rights and Biomedicine and its Additional Protocol to the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine, on the Prohibition of Cloning Human Being appear to ban SCNT of human beings. Of the Council's 45 member states, the Convention has been signed by 31 and ratified by 18. The Additional Protocol has been signed by 29 member nations and ratified by 14.

The UN is currently against all forms of human cloning.

See also

  • Stem cell research
  • Stem cell controversy
    Stem cell controversy
    The stem cell controversy is the ethical debate primarily concerning the creation, treatment, and destruction of human embryos incident to research involving embryonic stem cells. Not all stem cell research involves the creation, use, or destruction of human embryos...

  • Embryogenesis
    Embryogenesis
    Embryogenesis is the process by which the embryo is formed and develops, until it develops into a fetus.Embryogenesis starts with the fertilization of the ovum by sperm. The fertilized ovum is referred to as a zygote...

  • In vitro fertilisation
    In vitro fertilisation
    In vitro fertilisation is a process by which egg cells are fertilised by sperm outside the body: in vitro. IVF is a major treatment in infertility when other methods of assisted reproductive technology have failed...

  • Cloning
    Cloning
    Cloning in biology is the process of producing similar populations of genetically identical individuals that occurs in nature when organisms such as bacteria, insects or plants reproduce asexually. Cloning in biotechnology refers to processes used to create copies of DNA fragments , cells , or...

  • New Jersey legislation S1909/A2840
    S1909/A2840
    S1909/A2840 is a bill that was passed by the New Jersey legislature in December 2003, and signed into law by Governor James McGreevey on January 4, 2004, that permits human cloning for the purpose of developing and harvesting human stem cells...

  • Rejuvenation
    Rejuvenation (aging)
    Rejuvenation is the hypothetical reversal of the aging process.Rejuvenation is distinct from life extension. Life extension strategies often study the causes of aging and try to oppose those causes in order to slow aging...


External links