Stem Cell Manipulation
28 Oct 2003
There is currently much controversy over the use of embryonic stem cells (ESCs) in biomedical research. Stem cells are "unspecialised" cells, which have the potential to develop into almost any cell in the body. A large part of the controversy surrounding stem cells concerns the use of human embryos and the theoretical possibility that the technology could be used to clone humans. These articles review the different types of stem cell research and issues associated with the feasibility and potential use of a number of types of procedure involving stem cells.
Cloning The process of therapeutic cloning (also called somatic cell nuclear transfer or nuclear transplantation), involves transferring a nucleus from an adult donor cell into an egg cell which has had the nucleus removed. The nucleus contains all the DNA (genetic material) and information the cell needs to grow and multiply. This procedure tricks the DNA into reactivating embryonic genes and restarting embryo development. The new embryo (with the donor nucleus) has the potential to produce a genetically identical infant (a clone), to the individual who has supplied the nucleus, if transferred to the womb of a female "host". This process is known as reproductive cloning and was used to clone Dolly the sheep.
If the newly formed embryo is not implanted into a womb and is grown in "culture" (a cell model, in a laboratory) then the embryo produces ESCs, that have the potential to become any, or almost any, type of cell present in the adult body, such as nerve cells. Because stem cells are genetically identical to the donor cells, in principal, cells with therapeutic usefulness could be removed and transplanted into patients. This would also avoid the need to suppress the immune system (as in organ transplantation), to prevent rejection.
Cloned animals - reproductive cloning Most cloned embryos die soon after implantation in the womb or during pregnancy. Only a few survive to birth or beyond. Cloned animals which survive to birth often have common abnormalities which are not related to the type of donor cell used. These can be present initially as heart, kidney or brain defects or emerge later in life, such as obesity, premature death and tumour growth. These are thought to arise from faulty reprogramming when the adult nucleus is transplanted into the egg cell.
Therapeutic cloning Reproductive cloning is used to generate a cloned embryo which can be implanted into a female to produce a cloned offspring. Nuclear transplantation is different from therapeutic cloning in that the embryo is not implanted into a womb. Instead the embryo is grown in the laboratory and produces embryonic stem cells which can be "harvested" to create an "embryonic stem cell line". These can produce millions of ESCs that can (potentially) be used for cell replacement.
Embryonic Vs Adult stem cells Stem cells have also been found in adults in a range of places in the body, including the brain. However there is currently much discussion about adult stem cells (ASCs) and their usefulness in comparison to ESCs. ESCs have been shown to generate all cells whereas ASCs have not shown the same potential. The majority of brain tissue for example, cannot be produced from ASCs, therefore some cell replacement therapies are likely to need ESCs. ASCs are also hard to locate and difficult to grow in the laboratory. They also cannot easily be genetically manipulated to correct for genetic defects. One important exception however is the recent isolation of cells called "multipotent adult progenitor cells", which have recently been isolated from bone marrow and have the potential to differentiate into any cell.
The overall goal of stem cell therapy is to generate cells which can be used for transplantation to replace lost tissue, including nerve cells in neurological diseases, such as MS. Eventually it may be possible to avoid the use of ESCs by reprogramming adult cells directly, but the authors highlight the need to be able to investigate the potential for the therapy by being able to use ESCs.
These reports were published in the New England Journal of Medicine, 2003, vol. 349, no. 3, pages 211-212 and 275-286.
Stem cell use and regulations
The policy on stem cell use and regulations about the use of such cells are unclear and vary from country to country. These articles review the new policies and many issues surrounding this important topic. It also highlights the many "grey areas" still to be addressed.
The European Union (a group of European countries working together) is set to change the rules on stem cell use, allowing researchers to use EU funds to carry out stem cell studies using embryos left over from in vitro ("test tube") fertilisation. A vote on changing this policy is due towards the end of September. Despite this, there have already been experiments carried out in America, with animals and humans, using stem cells. Although scientists are careful to stress that this type of cell therapy is years down the road, the authors highlight that many doctors automatically assume that because stem cells are not drugs they don't require regulation or assessment in clinical trials. The case of a 57-year old man with Parkinson's Disease who received implants of new neurones in one side of his brain, is highlighted, as are patients with damaged spinal discs who received bone-forming stem cells from surgeons in Ohio, USA.
However, some researchers are stressing that using stem cells to treat patients, before full laboratory studies and safety checks have been carried out, could have very serious consequences. The possibility of hospitals offering these largely untested treatments has caused widespread concern and highlights the need for clear legislation. In addition the rules about stem cell use have not been made clear to doctors and researchers and the amount of cell manipulation allowable before a therapy, must be clear and regulated.
The report stresses that stem cell therapies will need to be tested for safety and effectiveness, in the same way that medicines are, before their potential use in mainstream therapy. This is emphasised as being especially important, as stem cells, unlike medicines, which are used periodically, are likely to be permanent additions, to the body.
This report was published in New Scientist, 19th July 2003, page 24 and Nature, 10th July vol. 424, page 117.
If the newly formed embryo is not implanted into a womb and is grown in "culture" (a cell model, in a laboratory) then the embryo produces ESCs, that have the potential to become any, or almost any, type of cell present in the adult body, such as nerve cells. Because stem cells are genetically identical to the donor cells, in principal, cells with therapeutic usefulness could be removed and transplanted into patients. This would also avoid the need to suppress the immune system (as in organ transplantation), to prevent rejection.
Cloned animals - reproductive cloning Most cloned embryos die soon after implantation in the womb or during pregnancy. Only a few survive to birth or beyond. Cloned animals which survive to birth often have common abnormalities which are not related to the type of donor cell used. These can be present initially as heart, kidney or brain defects or emerge later in life, such as obesity, premature death and tumour growth. These are thought to arise from faulty reprogramming when the adult nucleus is transplanted into the egg cell.
Therapeutic cloning Reproductive cloning is used to generate a cloned embryo which can be implanted into a female to produce a cloned offspring. Nuclear transplantation is different from therapeutic cloning in that the embryo is not implanted into a womb. Instead the embryo is grown in the laboratory and produces embryonic stem cells which can be "harvested" to create an "embryonic stem cell line". These can produce millions of ESCs that can (potentially) be used for cell replacement.
Embryonic Vs Adult stem cells Stem cells have also been found in adults in a range of places in the body, including the brain. However there is currently much discussion about adult stem cells (ASCs) and their usefulness in comparison to ESCs. ESCs have been shown to generate all cells whereas ASCs have not shown the same potential. The majority of brain tissue for example, cannot be produced from ASCs, therefore some cell replacement therapies are likely to need ESCs. ASCs are also hard to locate and difficult to grow in the laboratory. They also cannot easily be genetically manipulated to correct for genetic defects. One important exception however is the recent isolation of cells called "multipotent adult progenitor cells", which have recently been isolated from bone marrow and have the potential to differentiate into any cell.
The overall goal of stem cell therapy is to generate cells which can be used for transplantation to replace lost tissue, including nerve cells in neurological diseases, such as MS. Eventually it may be possible to avoid the use of ESCs by reprogramming adult cells directly, but the authors highlight the need to be able to investigate the potential for the therapy by being able to use ESCs.
These reports were published in the New England Journal of Medicine, 2003, vol. 349, no. 3, pages 211-212 and 275-286.
Stem cell use and regulations
The policy on stem cell use and regulations about the use of such cells are unclear and vary from country to country. These articles review the new policies and many issues surrounding this important topic. It also highlights the many "grey areas" still to be addressed.
The European Union (a group of European countries working together) is set to change the rules on stem cell use, allowing researchers to use EU funds to carry out stem cell studies using embryos left over from in vitro ("test tube") fertilisation. A vote on changing this policy is due towards the end of September. Despite this, there have already been experiments carried out in America, with animals and humans, using stem cells. Although scientists are careful to stress that this type of cell therapy is years down the road, the authors highlight that many doctors automatically assume that because stem cells are not drugs they don't require regulation or assessment in clinical trials. The case of a 57-year old man with Parkinson's Disease who received implants of new neurones in one side of his brain, is highlighted, as are patients with damaged spinal discs who received bone-forming stem cells from surgeons in Ohio, USA.
However, some researchers are stressing that using stem cells to treat patients, before full laboratory studies and safety checks have been carried out, could have very serious consequences. The possibility of hospitals offering these largely untested treatments has caused widespread concern and highlights the need for clear legislation. In addition the rules about stem cell use have not been made clear to doctors and researchers and the amount of cell manipulation allowable before a therapy, must be clear and regulated.
The report stresses that stem cell therapies will need to be tested for safety and effectiveness, in the same way that medicines are, before their potential use in mainstream therapy. This is emphasised as being especially important, as stem cells, unlike medicines, which are used periodically, are likely to be permanent additions, to the body.
This report was published in New Scientist, 19th July 2003, page 24 and Nature, 10th July vol. 424, page 117.
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