EUROPEAN  TISSUE  REPAIR  SOCIETY

By allowing research on stem cells from sacrificed human embryos today - the future holds the promise of being able to grow a number of different tissues to generate new life saving therapies. The issues are controversial involving ethics, science, politics and the creation of life itself.

Research at any stage on human embryo is a violation of the religious conviction of a large number of people. In addition, research involving the potential creation of life, might be abused in some countries. Then why are many scientists still interested in working with human stem cells and specifically in stem cells from human embryos?
Many diseases and disorders result from disruption of cellular function or destruction of tissues of the body. Today, the supply of donated organs and tissue that are used for repair is by far outnumbered by the need. This is where stem cells might fill a role by offering a renewable source of replacement cells and tissues to treat a number of diseases, conditions or disabilities. Early demonstrations in research laboratories include the treatment of spinal cord injury, stroke, burns, heart disease, osteoarthritis, rheumatoid arthritis, diabetes, and Parkinsons's and Alzheimer diseases.

One way to address this dilemma of ethics versus human benefit has been proposed by the bioethicist George Annas, Chair of the Health Law Department at Boston University's School of Public Health. 'Only genetic parents should determine weather embryos created through in vivo fertilisation are "excess" and not needed for reproduction. Parents could choose to donate their embryos to another couple, approve of their destruction, pay for indefinite cryopreservation, or after informed authorisation, donate them to research.'
There are many other suggestions about how to tackle this problem and there will certainly be more. One thing is sure; the race using engineering, of and with stem cells, towards the regeneration of human tissue is on. Stem cells are something that all clinicians or scientists involved in Tissue engineering will be asked about by their friends, patients or students.

What is a stem cell?
Stem cells are sources from which all the 'branches' of an organism are derived. An excellent review entitled 'Stem Cells: Scientific Progress and Future Research Directions' (June 2001) can be downloaded from:

http://www.nih.gov/news/stemcell/scireport.htm

Here it is explained that the stem cells have 'potential' either capable of becoming any tissue, or structure of the organism or indeed a new organism (Totipotential or toti-potent-), or open to diverse development (pluripotential or pluripotent-) but short of being able to generate a whole animal. Both totipotential and pluripotential stem cells might be used to develop various tissues such as neural tissue, liver cells or skin cells for therapeutic applications.
The human stem cell of all human stem cells is the fertilised egg, a zygote having a unique 46-chromosome endowment, half of which is contributed by a genetic father and half by a mother. This is an utterly unique cell, coded with all the information that makes us into individuals.

As this zygote replicates geometrically after conception, in the early stages, all its cells are totipotential. One of the microscopic cells can be removed without affecting the rest and each cell carries the entire genetic complement that could become an individual - or any sort of tissue into which it might be directed to develop.

UNLIMITED capability is found at early stages of development with totipotent cells.
Later stages may provide pluripotent cells capable of giving most types of tissues.

Further development into the blastocyst stage involves differentiation and therefore their potential is not total - they are now pluripotent. The pluripotent stem cells that can also be found in the fœtus undergo further specialisation into tissue specific stem cells that are committed to give rise to cells that have a particular function. An example of this is bone marrow stem cells that give rise to red blood cells, white blood cells and platelets. These more specialised cells are called multipotent.

Your friends or patients might argue that since all cells in a human body have the individual's entire and unique genetic code, what is so special about stem cells? The answer, of course, is yes, all cells in the body do have the same genetic code, but most of these cells are, however, committed, or differentiated, in such a way as to replicate only as skin or liver or neural tissue. They are programmed only be able to express certain parts of their genetic information. Totipotent or pluripotent stem cells do not have this limitation. Even mature organisms have stem cells, usually in the bone marrow. It is thought that these might be as serviceable as embryonic stem cells; but because of questions largely related to the age of an organism, they are not as desirable as the fresh cells of an embryo. Recent research suggests, however, that there might be a possibility that any cell of an organism can be coaxed into the totipotential stage.

From where can we get embryonic stem cells?
The problem is to find a source of stem cells. The early human embryo and fœtal tissue are excellent sources for stem cells. To avoid immune rejection, however, they should ideally derive from the embryo or umbilical cord of the patient to be treated. Here one could envisage a future when stem cells from each new born baby's umbilical cord, that otherwise is discarded as waste, are kept by cryopreservation until the moment the patient needs these cells. Such initiatives are already underway.

Alternatively, there is a way that cells could be genetically matched to the patient, to avoid rejection. Nuclear transfer, the central technology of cloning (Dolly the Sheep technology), could in principle provide matched cells, because a nucleus derived from a patient's own cell sample could be used to replace the nucleus in embryonic stem cell lines that are grown in culture. Yet there could still be show-stoppers. It may turn out that cultured embryonic stem cells descended from cloned embryos lack the full potential of those from natural embryos. Indeed, many embryos resulting from nuclear transfer have defects, possibly because gene expression is abnormal in embryos that lack two genetic parents. This is a major area of concern. It will be vital to avoid generating tumours in the newly grown tissues.

When an acceptable source is available there are still major hurdles First the ability to grow and expand the number of human stem cells is currently limited. Once better techniques of cell culture become available, limitless quantities of 'universal donor' stem cells will be reality. Second, we don't yet know very much about how to direct cultured stems cells down alternative tissue development pathways. This will be a task for current and future Tissue engineers.

Implications of restricted public funding
Recent legislation in the USA has banned the cloning of new human embryonic stem cells, although existing lines can be used. The reasons are a heady mix of politics and ethics. Given the potential of these technologies, restricting legislation might channel all development into private companies. A lack of public funding for emerging technologies that may generate considerable return on investment will result in only a few companies holding all the patents in this area. It is likely that this situation will not be the most beneficial for the long-term development of these emerging technologies. Different countries have taken alternative approaches. In the UK research on stem cells will be permissible under specific guidelines. Very good information on the science, ethics and public discussion on the use of stem cells is available from the Royal Society in London, at:

http://www.royalsoc.ac.uk/files/statfiles/document-148.pdf http://www.royalsoc.ac.uk/policy/index.html
http://www.royalsoc.ac.uk/royalsoc/new_fr.htm

J. G. Hilborn PhD

Printed by kind permission of the European Tissue Engineering Society (ETES) from their October 2001 Newsletter, from Dr Robin Martin.